Postoperatieve pijn

Initiatief: NVA Aantal modules: 68

Epidurale analgesie bij abdominale chirurgie

Uitgangsvraag

Wat is de plaats van epidurale analgesie bij zorg voor kinderen die een abdominale chirurgische ingreep ondergaan?

Aanbeveling

Overweeg het gebruik van epidurale analgesie postoperatief bij kinderen na een open abdominale ingreep ter vervanging van intraveneuze toediening van opioïden of in het kader van multimodale analgesie.

 

Neem daarbij in overweging:

  • de mogelijke voordelen van een lager postoperatief opioïdengebruik
  • langdurige nabeademing op kinder-IC
  • de technische expertise van de kinderanesthesioloog
  • de ervaring bij de acute pijn service

Overwegingen

Voor- en nadelen van de interventie en de kwaliteit van het bewijs

Er is literatuuronderzoek verricht naar de gunstige en ongunstige effecten van epidurale analgesie in vergelijking met intraveneus opioïden bij kinderen die een abdominale chirurgische ingreep ondergaan. Er zijn vier RCT’s en zes observationele studies geïncludeerd in de literatuursamenvatting. De operaties die de kinderen ondergingen waren divers, maar het ging in alle gevallen om open abdominale chirurgie (geen laparoscopische ingrepen). Het aantal patiënten per studiearm varieerde van 25 tot 30 in de RCT’s en 22 tot 151 in de observationele studies. Sommige studies includeerden zeer jonge kinderen (gemiddelde leeftijd van 6 weken of 45 dagen) en in andere studies waren de kinderen wat ouder (bijna 9 jaar). In een deel van de studies was het geslacht van de kinderen niet beschreven. Daar waar het wel beschreven was, varieerde het percentage jongens van 38 tot 70 procent.

 

De studies waren doorgaans klein en hadden methodologische beperkingen. Hierdoor was er risico op vertekening van resultaten (risk of bias). Aanvullend werd soms de optimale populatiegrootte (OIS) niet behaald door kleine aantallen en een enkele keer waren resultaten inconsistent tussen studies. Daarom is de bewijskracht voor alle uitkomstmaten in meer of mindere mate afgewaardeerd.

 

Postoperatieve pijn op 0, 6 en 24 uur en angst was gedefinieerd als cruciale uitkomstmaat. Voor postoperatieve pijn was de bewijskracht zeer laag. Op basis van de geïncludeerde literatuur kunnen geen conclusies getrokken worden. Voor angst was geen literatuur beschikbaar. Daarmee komt de totale bewijskracht uit op zeer laag.

 

Postoperatief gebruik van opioïden, angst, duur van ziekenhuisopname, adverse events, urineretentie en tijd tot eerste orale voeding waren gedefinieerd als belangrijke uitkomstmaten. Voor angst en adverse events werd geen bewijs gevonden. Voor de overige uitkomstmaten is, vanwege boven benoemde redenen, de bewijskracht van ook deze literatuur zeer laag.

 

Samenvattend kan de literatuur onvoldoende richting geven aan de besluitvorming. De aanbeveling is daarom gebaseerd op aanvullende argumenten waaronder expert opinie, waar mogelijk aangevuld met (indirecte) literatuur.

 

Epidurale analgesie bij kinderen en met name in de groep kinderen jonger dan één jaar oud, wordt met name toegepast in de kindercentra waar voldoende ervaring is met het inbrengen van epidurale katheters bij kinderen, en waar er ook expertise is bij de acute pijn service met de opvolging van kinderen met een epiduraal. In ervaren handen (technische expertise van de kinderanesthesioloog, ervaring bij de APS) wordt epidurale analgesie gezien als een veilige methode van postoperatieve pijnstilling bij kinderen. Ook in de genoemde studies zijn er geen ernstige bijwerkingen of adverse events gezien, zoals epiduraal hematoom, epiduraal abces/infectie of zenuwschade.

 

Uit de literatuur blijkt er weinig bewijskracht voor een betere postoperatieve pijnstilling ten opzichte van systemische analgesie bij kinderen, alhoewel de studies zoals aangegeven vaak klein zijn van opzet en er diverse groepen patiënten en operaties zijn onderzocht. Wel zijn de pijnscores gemiddeld laag bij kinderen die epidurale katheter kregen als postoperatieve pijnstilling, wat aangeeft dat er een goede postoperatieve analgesie was bij deze kinderen.

Een paar studies rapporteren een klinisch relevante reductie in opioïde behoefte in de kinderen met epidurale analgesie, echter was de bewijskracht van deze studies zeer laag. Een reductie in opioïde behoefte zou voor met name jonge kinderen een voordeel zijn ten aanzien van bijwerkingen zoals ademhalingsdepressie, wat bij zeer jonge kinderen kan leiden tot lange duur van nabeademing postoperatief.

Voor subgroepen van kinderen, zoals kinderen met een kans op beademing postoperatief, is het te overwegen te kiezen voor epidurale analgesie. Daarnaast kan er in het kader van de multimodale pijnbestrijding gekozen worden voor epidurale analgesie, evenals bij patiënten waarbij opioïden ongewenst zijn i.v.m. het risico op ileus postoperatief.

 

In de gevonden literatuur zijn er geen studies die hebben onderzocht wat de toegevoegde waarde was van epidurale pijnstilling na scopische abdominale ingrepen (laparoscopie): er werden enkel studies gevonden die pijnstilling na open abdominale ingrepen onderzochten. De anesthesioloog kan bij een laparoscopische ingreep de conversiekans naar laparotomie meenemen in de beslissing om al dan niet te kiezen voor een epiduraal. Mocht er een conversie naar laparotomie plaatsvinden, kan er ook voor worden gekozen om direct postoperatief, voor de uitleiding van de anesthesie, alsnog een epiduraal te plaatsen, al valt het voordeel van het reduceren van opioïden peroperatief dan weg.

 

Waarden en voorkeuren van patiënten (en evt. hun verzorgers)

Ouders en kinderen dienen te worden voorgelicht over de mogelijke risico’s van epidurale analgesie, zoals de (zeldzame) mogelijkheid van durale punctie, infectie en epiduraal hematoom. De kans op het optreden van deze complicaties is zeer klein, maar moeten worden meegenomen in de afweging voor het kiezen van epidurale analgesie danwel systemische analgetica. Daarnaast is het van belang de mogelijkheid te bespreken van het falen van de epiduraal, door technische problemen (kinken van de katheter, luxatie) of anderszins.

 

Kosten (middelenbeslag)

De kosten van epidurale pijnstilling postoperatief zijn niet verschillend ten opzichte van systemische analgetica postoperatief. Aangezien de ligduur niet significant korter is met epidurale pijnbestrijding is dit ook niet bijdragend in de keuze voor epidurale pijnbestrijding.

 

Aanvaardbaarheid, haalbaarheid en implementatie

Het inbrengen van een epiduraalkatheter wordt met name uitgevoerd door ervaren (kinder)anesthesiologen. Het lijkt minder te worden toegepast in algemene ziekenhuizen, wat vooral te maken heeft met de lokale expertise.

 

Rationale van de aanbeveling: weging van argumenten voor en tegen de interventies

De literatuur is onzeker over het effect van epidurale analgesie ten opzichte van systemische analgesie (opioïden intraveneus) op postoperatieve pijnstilling bij kinderen na een open abdominale operatie. De studies gaven wel een lage gemiddelde pijnscore aan bij kinderen met epidurale pijnstilling postoperatief.

De incidentie van ernstige adverse events van epidurale analgesie bij kinderen, zoals epiduraal hematoom, infectie of abces, of zenuwschade, is zeer laag bij kinderen. Andere adverse events, zoals blaasretentie en tijd tot de eerste orale voeding, lijken niet klinisch relevant verschillend te zijn ten opzichte van opioïden (Walker, 2018; Polaner, 2012).

Epidurale analgesie bij kinderen is een veilige methode van pijnstilling postoperatief, mits uitgevoerd door ervaren professionals en met goede postoperatieve opvolging door een acute pijn service (APS) met ervaring bij kinderen.

 

Gezien de mogelijkheid om de toediening van opioïden te kunnen reduceren, kan epidurale analgesie ter overweging zijn als men de bijwerkingen van opioïden wil vermijden, zoals bij jonge kinderen met het risico op ademhalingsdepressie, of in het kader van multimodale pijnstilling. De aanbeveling geldt voor open abdominale ingrepen. Bij laparoscopische ingrepen kan de conversiekans naar een laparotomie worden meegenomen in de overweging van de anesthesioloog om een epiduraal te plaatsen.

Onderbouwing

Bij kinderen die een abdominale ingreep ondergaan wordt epidurale analgesie steeds meer toegepast. Voorheen was men hiermee terughoudend: de epidurale katheter moet (anders dan bij volwassenen) bij kinderen onder anesthesie worden ingebracht. Dat betekent dat de risico’s bij het plaatsen (zoals het optreden van perforatie van de dura mater, of zenuwschade) wat groter kunnen zijn dan bij volwassenen, ook omdat de afstand tot aan de epidurale ruimte uiteraard kleiner is en het weefsel vaak zachter is. Inmiddels is duidelijk uit de literatuur dat ook bij kinderen het plaatsen van een epiduraalkatheter veilig is in getrainde handen, al zijn de risico’s bij de jongste categorie kinderen (<6 maanden) nog steeds iets groter (Ecoffey, 2010; Walker, 2018; Polaner, 2012).

Een voordeel van de epiduraal kan zijn, naast goede pijnstilling postoperatief: het kunnen verlagen van de morfine, zodat de bijwerkingen van morfine/opioïden afnemen (ademhalingsdepressie, nausea en braken, snellere tijd tot eerste voeding) (Bhandari, 2005).

 

De vraag vanuit de praktijk is of de voordelen van een epiduraal bij kinderen wel zo groot zijn ten opzichte van bijvoorbeeld morfine intraveneus, dat dit de keuze voor de epiduraal rechtvaardigt.

 

Very low GRADE

The evidence is very uncertain about the effect of epidural analgesia on postoperative pain at 0 hours, 6 hours and 24 hours post-surgery compared with opioids in children undergoing abdominal surgery.

 

Source: Mansfield, 2021; Phelps, 2019; Bozkurt, 2003; Warmann, 2014

 

Very low GRADE

The evidence is very uncertain about the effect of epidural analgesia on opioid consumption 24 hours post-surgery compared with opioids in children undergoing abdominal surgery.

 

Source: Mansfield, 2021; Martin, 2019

The evidence is very uncertain about the effect of epidural analgesia on total postoperative opioid consumption compared with opioids in children undergoing abdominal surgery.

 

Source: Gannam-Somri, 2020

 

No GRADE

No evidence was found regarding the effect of epidural analgesia compared with opioids on anxiety in children undergoing abdominal surgery.

 

Source: -

 

Very low GRADE

The evidence is very uncertain about the effect of epidural analgesia on length of stay compared with opioids in children undergoing abdominal surgery.

 

Source: Mansfield, 2021; Phelps, 2019; Warmann, 2014; Wilson, 2001

 

Very low GRADE

The evidence is very uncertain about the effect of epidural analgesia on PONV compared with opioids in children undergoing abdominal surgery.

 

Source: Bozkurt, 2003; Wilson, 2001

 

 

No GRADE

No evidence was found regarding the effect of epidural analgesia compared with opioids on other adverse events in children undergoing abdominal surgery.

 

Source: -

 

Very low GRADE

The evidence is very uncertain about the effect of epidural analgesia on urinary retention compared with opioids in children undergoing abdominal surgery.

 

Source: Mansfield, 2021

 

Very low GRADE

The evidence is very uncertain about the effect of epidural analgesia on time to first oral feeding compared with opioids in children undergoing abdominal surgery.

 

Source: Mansfield, 2021; Phelps, 2019

 

Description of studies

Four RCTs and six observational studies were included in this literature summary.

As shown in table 1, studies were conducted in patients undergoing various surgeries.  Patients per arm varied from 25 to 30 in the RCTs and 22 to 151 in the observational studies. The mean age of studies varies from 6 weeks or 45 days to almost 9 years. The percentage of males was often not specified, but for the studies that did report the sex of the patients, the male percentage varied from 38 to 70%.

 

Table 1: Descriptives of included studies.

Author, year

 

Population (I/C), mean age; %M

Surgical procedure

Intervention

Control

RCTs

Somri, 2011

25/25; 6.4 weeks; n.s.

Elective primary gastro-intestinal surgery

Combined spinal-epidural anesthesia

General anesthesia with opioids

Gannam-Somri, 2020

28/30; 7.7 weeks; n.s.

Elective gastrointestinal surgery

Combined epidural‐general anesthesia

 

General anesthesia with opioids

Bozkurt, 2003

25/25; 6.6 years; 70% M

Major genitourinary

or abdominal operations

Single dose of epidural morphine

Morphine infusion + morphine bolus

Perova-Scharonova, 2021

26/25; 115 and 89 months; 38 and 44%

Surgery for appendicular peritonitis

Epidural anesthesia

Intravenous infusion of morphine

Observational studies

Mansfield, 2021

151/35; 6.7 and 8.8 years; n.s.

Laparotomy (thoracotomy results not included) in oncology hospital

Epidural anesthesia

No epidural anesthesia; intravenous patient-controlled analgesia

Martin, 2019

47/35; median 45 and 101 days; n.s.

Major abdominal surgery

Epidural anesthesia

No epidural anesthesia; i.v. opioids

Phelps, 2019

25/22; median 56.0 and 63.5 days;

Kasai porto-enterostomy for Biliary atresia

Epidural anesthesia

No epidural anesthesia

Relland, 2022

24/24; 33 weeks; 46 and 67%

Open abdominal surgery

Epidural anesthesia

No epidural anesthesia (systemic therapy only)

Warmann, 2014

40/40; 56 and 39 months; n.s.

Resection of an abdominal tumor

Epidural anesthesia

No epidural anesthesia; continuous i.v. opioids

Wilson, 2001

65/39; median 27 and 26 months; 52 and 54%

Nissen fundoplication, for documented pathological gastro-esophageal reflux

Epidural anesthesia

Continuous morphine infusion

Results

1. Postoperative pain

1.1 Postoperative pain at 0 to 24 hours post-surgery

One observational study reported postoperative pain at 0 hours post-surgery.

Mansfield (2021) used the FLACC scale for children with age 1 month to 3 years, the Wong–Baker Faces Pain Rating Scale for ages 3 to 7 years and the Numeric Pain Rating Scale for children of 7 years of age and older. At 0 to 6 hours post-surgery, the mean (SD) pain score was 1.22 (SD 0.99) in the intervention group and 1.75 (SD 1.33) in the control group. The mean difference (MD) of -0.53 (95% CI -1.00 to -0.06) is not considered clinically relevant.

 

1.2 Postoperative pain at 6 hours post-surgery

One observational study reported postoperative pain at 6 hours post-surgery.

Phelps (2019) used the FLACC scale to report postoperative pain. At 6 hours post-surgery, the median (IQR) pain score was 0.5 (IQR 0 to 2.0) in the intervention group and 1.7 (IQR 0.2 to 3.5) in the control group. This median difference of 1.2 point is considered clinically relevant and is in favor of the intervention group.

 

1.3 Postoperative pain at 24 hours post-surgery

One RCT (Bozkurt, 2003) reported postoperative pain at 24 hours post-surgery. Results were only presented in a figure and were therefore read from the box plots. The FACES pain score was reported, which was assessed by nurses as of five face drawing with 0 indicating no hurt and 5 indicating the worst hurt. The pain score was 2.0 in the intervention group and 1.6 in the control group. This difference of 0.4 is not considered clinically relevant.

 

Three observational studies reported postoperative pain at 24 hours post-surgery. As this outcome measure was also reported by a RCT, these results were not graded for the level of evidence.

 

Mansfield (2021) used the FLACC scale for children with age 1 month to 3 years, the Wong–Baker Faces Pain Rating Scale for ages 3 to 7 years and the Numeric Pain Rating Scale for children of 7 years of age and older. At 24 hours post-surgery, the average pain scores were 1.87 (SD 1.25) in the intervention group and 2.19 (SD 0.95) in the control group. The MD was -0.32 (95% CI -0.69 to 0.05), which is not considered a clinically relevant difference.

 

Phelps (2019) used the FLACC scale to report postoperative pain. At 18 to 24 hours post-surgery, the median pain scores were 0 (IQR 0 to 2) in the intervention group and 1.8 (IQR 1 to 3.8) in the control group. This median difference of -1.8 point is considered clinically relevant and is in favor of the intervention group.

 

Warmann (2014) used the ‘pain score’, not further specified. At 24 hours post-surgery, the mean pain was 2.90 (range 2.22 to 3.58) in the intervention group and 3.57 (range 2.94 to 4.20) in the control group. Based on this data, the confidence intervals could not be calculated. The mean difference of -0.67 points is not considered clinically relevant.

 

2. Postoperative opioid consumption

2.1 Postoperative opioid consumption at 24 hours post-surgery

Two observational studies reported opioid consumption at 24 hours post-surgery.

 

Mansfield (2021) reported that the total opioid consumption on the first postoperative day was 0.33 (SD 0.3) OME/kg/day in the intervention group and 0.93 (SD 1.53) OME/kg/day in the control group. The MD was -0.60 OME/kg/day, which is considered a clinically relevant difference in favor of the intervention group.

 

Martin (2019) reported that the median opioid administration in the first 24 postoperative hours was 0.24 mg/kg (IQR 0.09 to 0.44) in the intervention group and 0.34 mg/kg (IQR 0.11 to 0.5) in the control group. The median difference of -0.10 mg/kg is considered a clinically relevant difference in favor of the intervention group.

 

2.2 Total postoperative opioid consumption

One RCT (Gannam-Somri, 2020) reported that the median total opioid (fentanyl) consumption was 55 μg (range 40 to 200) in the intervention group and 230 μg (range 60 to 750) in the control group. The median difference of -175 μg is considered clinically relevant in favor of the intervention group.

 

One observational study reported postoperative pain at 24 hours post-surgery. As this outcome measure was also reported by an RCT, these results were not graded for the level of evidence.

 

Relland (2022) reported that the average postoperative cumulative opioid consumption per patient over the entire study period was 3.2 mg/kg in the intervention group and 19.7 mg/kg in the control group. The MD was 16.5 mg/kg, which was considered a clinically relevant difference in favor of the intervention group.

 

3. Anxiety

None of the included studies reported peri-operative or postoperative anxiety.

 

4. Length of stay

Four observational studies reported the length of stay.

 

Mansfield (2021) reported that the median (IQR) length of hospital stay was 4 days (IQR 4 to 6) in the intervention group and 5 days (IQR 4 to 6) in the control group. This difference of -1 day was considered clinically relevant and was in favor of the intervention group.

 

Phelps (2019) reported that the median (IQR) length of hospital stay was 6 days (IQR 5 to 7) in the intervention group and 8 days (IQR 6.3 to 11) in the control group. This difference of -2 days was considered clinically relevant and was in favor of the intervention group.

 

Warmann (2014) reported that the mean length of hospital stay was 11.7 days (95% CI 10.2 to 13.5) in the intervention group and 10.4 days (95% CI 8.8 to 12.3) in the control group. This difference of 1.3 days was considered clinically relevant and was in favor of the control group.

 

Wilson (2001) reported that the mean length of hospital stay was 8 days (range 3 to 53) in the intervention group and 13 days (range 3 to 53) in the control group. This difference of -5 days was considered clinically relevant and was in favor of the intervention group.

 

5. Adverse events (epidural hematoma, epidural infection (abces), nerve damage, failure, motor blockade, PONV)

One RCT and four observational studies described adverse events. The only adverse event of interest reported was PONV. Therefore, PONV is the only outcome that is graded for the level of evidence.

 

5.1 PONV

Bozkurt (2003) reported that five patients in the epidural group vomited several times and three others vomited once at 7 hours (± 2) after epidural morphine administration. In the infusion group three patients vomited several times and five others vomited once after 7(± 4) hours of morphine infusion (RR 1.67; 95% CI 0.45 to 6.24).

 

Wilson (2001) reported postoperative vomiting. In the epidural group, 36 out of 65 (55%) experienced vomiting, compared to 19 out of 39 (49%) in the opioid group (RR 1.14; 95% CI 0.77 to 1.68).

 

5.2 Other adverse events

Phelps (2019) reported that apnea and/or bradycardia occurred in 5 out of 25 (20%) patients in the intervention group, compared with 6 out of 22 (27%) patients in the control group.

In the intervention group, none of the patients required re-intubation following post-operative extubation or transfer to ICU. Some technical problems associated with catheters were reported. One epidural failed due to a kink and four catheters migrated out. One epidural was removed upon parental request.

 

Relland (2022) described that in both groups, no serious adverse event occurred.

 

Warmann (2014) described that no catheter-related complications occurred in the study group. Also, no bleeding, allergic reactions, neurological complications and infectious complications occurred.

 

Wilson (2001) did not report absolute values, but described that in 25% of the intervention group, episodes of hypotension occurred, compared with 10% of the control group. The difference was described as statistically non-significant, but without absolute data this cannot be checked, and the clinical relevance cannot be interpreted.

 

6. Urinary retention

One observational study reported urinary retention.

Mansfield (2021) reported that the median time with a urinary catheter was 3 days (IQR 3 to 4) in the intervention group and 6 days (IQR 1 to 4) in the control group. This median difference of 3 days was considered a clinically relevant difference and was in favor of the intervention group.

 

7. Time to first oral feeding

Two observational studies reported the time to first oral feeding.

 

Mansfield (2021) reported that the median time to resumption of regular diet was 4 days (IQR 3 to 4) in the intervention group and 3 days (2 to 5) in the control group. This median difference of 1 day was considered clinically relevant and in favor of the control group.

 

Phelps (2019) reported that the median time to first oral feed was 3 days (IQR 2 to 4) in the intervention group and 3 days (IQR 2 to 3) in the control group. There was no difference between groups.

 

One RCT and one observational study described the time to full enteral nutrition. As this was not the defined outcome, these results were not graded for level of evidence.

Gannam‐Somri (2020, RCT) reported that the median postoperative time to tolerance of full enteral nutrition was 4.0 days (IQR 1.0) in the intervention group and 8.0 days (IQR 2.0) in the control group. This median difference of 4 days was considered a clinically relevant difference and was in favor of the intervention group.

Warmann (2014, observational) reported that the mean time to complete oral feeding was 3.91 days (95% CI 3.11 to 4.90) in the intervention group and 3.64 days (95% CI 2.86 to 4.62) in the control group. This difference of 0.27 was not considered clinically relevant.

 

Level of evidence of the literature

The level of evidence regarding the outcome measure postoperative pain 0 hours post-surgery started at low and was downgraded by 1 level because of study limitations (risk of bias) and not meeting the optimal information size (imprecision, -1). The level of evidence regarding the outcome measure postoperative pain 0 hours post-surgery is very low.

The level of evidence regarding the outcome measure postoperative pain 6 hours post-surgery started at low and was downgraded by 1 level because of study limitations (risk of bias) and not meeting the optimal information size (imprecision, -1). The level of evidence regarding the outcome measure postoperative pain 6 hours post-surgery is very low.

The level of evidence regarding the outcome measure postoperative pain 24 hours post-surgery started at high and was downgraded by 3 levels because of study limitations (risk of bias, -1) and not meeting the optimal information size (imprecision, -2). The level of evidence regarding the outcome measure postoperative pain 24 hours post-surgery is very low.

 

The level of evidence regarding the outcome measure opioid consumption 24 hours post-surgery started at low and was downgraded by 1 level because of study limitations (risk of bias, -1) and not meeting the optimal information size (imprecision, -1); publication bias. The level of evidence regarding the outcome measure opioid consumption 24 hours post- surgery is very low.

The level of evidence regarding the outcome measure total postoperative opioid consumption started at high and was downgraded by 3 levels because of study limitations (risk of bias, -1) and not meeting the optimal information size (imprecision, -2). The level of evidence regarding the outcome measure total postoperative opioid consumption is very low.

 

No evidence was available for the outcome measure anxiety.

 

The level of evidence regarding the outcome measure length of stay started at low and was downgraded by 1 level because of study limitations (risk of bias, -1); conflicting results (inconsistency, -1) and not meeting the optimal information size (imprecision, -1). The level of evidence regarding the outcome measure length of stay is very low.

 

The level of evidence regarding the outcome measure PONV started at low and was downgraded by 1 level because of because of study limitations (risk of bias, -1); and a small number of reported events (imprecision, -1). The level of evidence regarding the outcome measure PONV is very low.

 

Limited evidence was available for the outcome measure other adverse events.

 

The level of evidence regarding the outcome measure urinary retention started at low and was downgraded by 1 level because of study limitations (risk of bias, -1) and not meeting the optimal information size (imprecision, -1). The level of evidence regarding the outcome measure urinary retention is very low.

 

The level of evidence regarding the outcome measure time to first oral feeding started at low and was downgraded by 1 level because of study limitations (risk of bias, -1) and not meeting the optimal information size (imprecision, -1). The level of evidence regarding the outcome measure time to first oral feeding is very low.

A systematic review of the literature was performed to answer the following question:

What is the (in)effectiveness of epidural analgesia compared with opioids on postoperative pain, anxiety, postoperative opioid consumption, adverse events, length of stay, urinary retention and time to first oral feeding in children undergoing an abdominal surgical procedure?

P: Children undergoing an abdominal surgical procedure
I: Epidural analgesia + standard care
C: Opioids + standard care
O:

Postoperative pain

Anxiety

Postoperative opioid consumption

Adverse events

Length of stay

Urinary retention

Time to first oral feeding

Relevant outcome measures

The guideline development group considered postoperative pain as a critical outcome measure for decision making; and postoperative opioid consumption, anxiety, length of stay, adverse events, urinary retention and time to first oral feeding as an important outcome measure for decision making.

 

The working group defined the outcome measures as follows:

  • Postoperative pain à PACU / 0 hours, 6 and 24 hours (at rest; if nothing was reported about the condition in which pain was assessed (at rest or during mobilization) it was assumed pain was measured at rest)
  • Postoperative opioid consumption à 24 hours and total
  • Length of stay à length of stay in hospital in days or weeks
  • Adverse events à epidural hematoma, epidural infection (abscess), nerve damage, failure, motor blockade, postoperative nausea and vomiting (PONV)
  • Urinary retention à time requiring a urinary catheter in hours, days of weeks
  • Time to oral feeding à time to first oral feeding in hours, days of weeks

The working group defined one point as a minimal clinically (patient) important difference on a 10-point pain scale and 10 mm on a 100 mm pain scale.

Regarding postoperative opioid consumption, a difference of 20% (in OME/kg/d) between groups was considered clinically relevant. For dichotomous variables, a difference of 10% was considered clinically relevant (RR ≤0.91 or ≥1.10; RD 0.10).

For length of stay, urinary retention and time to first oral feeding a difference of one day was considered clinically relevant.

For continuous variables, a difference of 10% of the total scale was considered clinically relevant. For dichotomous variables, a difference of 10% was considered clinically relevant (RR ≤0.91 or ≥1.10; RD 0.10).

 

Search and select (Methods)

The databases [Medline (via OVID) and Embase (via Embase.com)] were searched with relevant search terms until 14-10-2022. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 425 hits. Studies were selected based on the following criteria:

1) Systematic review, RCT or observational study, 2) comparing epidural analgesia with opioids, 3) in children undergoing abdominal surgery, 4) reporting one of the relevant outcome measures, 5) N per arm ≥ 10 and 6) publication in English or Dutch.

A total of 37 studies were initially selected based on title and abstract screening. After reading the full text, 27 studies were excluded (see the table with reasons for exclusion under the tab Methods), and 10 studies were included.

 

Results

Four RCTs and six observational studies were included in the analysis of the literature. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.

 

In case an RCT reported the outcome measure, the level of evidence was assessed based on these results (starting at HIGH GRADE). In case no results from RCTs were available, results of observational studies were described, and level of evidence was assessed according to these results (starting at LOW GRADE).

  1. Bhandari V, Bergqvist LL, Kronsberg SS, Barton BA, Anand KJ, Group NTI. Morphine administration and short-term pulmonary outcomes among ventilated preterm infants. Pediatrics. Aug 2005;116(2):352-9. doi:116/2/352
  2. Bozkurt P, Kaya G, Yeker Y, Altintas F, Bakan M, Hacibekiroglu M, Kavunoglu G. Effects of systemic and epidural morphine on antidiuretic hormone levels in children. Paediatr Anaesth. 2003 Jul;13(6):508-14. doi: 10.1046/j.1460-9592.2003.01096.x. PMID: 12846707.
  3. Ecoffey C, Lacroix F, Giaufré E, Orliaguet G, Courrèges P; Association des Anesthésistes Réanimateurs Pédiatriques d'Expression Française (ADARPEF). Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF). Paediatr Anaesth. 2010 Dec;20(12):1061-9. doi: 10.1111/j.1460-9592.2010.03448.x. PMID: 21199114.
  4. Gannam-Somri L, Matter I, Hadjittofi C, Vaida S, Khalaily H, Hossein J, Somri M. Combined epidural-general anaesthesia vs general anaesthesia in neonatal gastrointestinal surgery: A randomized controlled trial. Acta Anaesthesiol Scand. 2020 Jan;64(1):34-40. doi: 10.1111/aas.13469. Epub 2019 Oct 7. PMID: 31506919.
  5. Mansfield SA, Woodroof J, Murphy AJ, Davidoff AM, Morgan KJ. Does epidural analgesia really enhance recovery in pediatric surgery patients? Pediatr Surg Int. 2021 Sep;37(9):1201-1206. doi: 10.1007/s00383-021-04897-z. Epub 2021 Apr 8. PMID: 33830298.
  6. Martin LD, Adams TL, Duling LC, Grigg EB, Bosenberg A, Onchiri F, Jimenez N. Comparison between epidural and opioid analgesia for infants undergoing major abdominal surgery. Paediatr Anaesth. 2019 Aug;29(8):835-842. doi: 10.1111/pan.13672. Epub 2019 Jun 23. PMID: 31140664.
  7. Perova-Sharonova V, Fesenko U. The Intestinal Barrier Function and Intra-Abdominal Pressure Depend on Postoperative Analgesia Technique in Children with Appendicular Peritonitis. Crit Care Res Pract. 2021 Aug 7;2021:6650361. doi: 10.1155/2021/6650361. PMID: 34413982; PMCID: PMC8369189.
  8. Phelps HM, Robinson JR, Chen H, Luckett TR, Conroy PC, Gillis LA, Hays SR, Lovvorn HN 3rd. Enhancing Recovery After Kasai Portoenterostomy With Epidural Analgesia. J Surg Res. 2019 Nov;243:354-362. doi: 10.1016/j.jss.2019.05.059. Epub 2019 Jul 2. PMID: 31277012; PMCID: PMC6773489.
  9. Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth Analg. Dec 2012;115(6):1353-64. doi:ANE.0b013e31825d9f4b [pii]
  10. Relland LM, Beltran R, Kim SS, Bapat R, Shafy S, Uffman J, Maitre NL, Tobias JD, Veneziano G. Continuous epidural chloroprocaine after abdominal surgery is associated with lower postoperative opioid exposure in NICU infants. J Pediatr Surg. 2022 Apr;57(4):683-689. doi: 10.1016/j.jpedsurg.2021.05.015. Epub 2021 May 29. PMID: 34154813.
  11. Somri M, Matter I, Parisinos CA, Shaoul R, Mogilner JG, Bader D, Asphandiarov E, Gaitini LA. The effect of combined spinal-epidural anesthesia versus general anesthesia on the recovery time of intestinal function in young infants undergoing intestinal surgery: a randomized, prospective, controlled trial. J Clin Anesth. 2012 Sep;24(6):439-45. doi: 10.1016/j.jclinane.2012.02.004. Epub 2012 Jul 2. PMID: 22762977.
  12. Walker BJ, Long JB, Sathyamoorthy M, et al. Complications in Pediatric Regional Anesthesia: An Analysis of More than 100,000 Blocks from the Pediatric Regional Anesthesia Network. Anesthesiology. Oct 2018;129(4):721-732. doi:10.1097/ALN.0000000000002372
  13. Warmann SW, Lang S, Fideler F, Blumenstock G, Schlisio B, Kumpf M, Ebinger M, Seitz G, Fuchs J. Perioperative epidural analgesia in children undergoing major abdominal tumor surgery--a single center experience. J Pediatr Surg. 2014 Apr;49(4):551-5. doi: 10.1016/j.jpedsurg.2013.10.025. Epub 2013 Nov 12. PMID: 24726111.
  14. Wilson GA, Brown JL, Crabbe DG, Hinton W, McHugh PJ, Stringer MD. Is epidural analgesia associated with an improved outcome following open Nissen fundoplication? Paediatr Anaesth. 2001 Jan;11(1):65-70. doi: 10.1046/j.1460-9592.2001.00597.x. PMID: 11123734.

Evidence table for intervention studies (randomized controlled trials and non-randomized observational studies [cohort studies, case-control studies, case series])

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

 

Follow-up

Outcome measures and effect size 4

Comments

Somri, 2011

Type of study:

RCT

 

Setting and country:

Single-center; Israel.

 

Funding and conflicts of interest:

“No external funding and no competing interests

are declared.”

infants who underwent elective primary gastro-intestinal surgery

 

Inclusion criteria:

  • infants who underwent
  • elective primary GI surgery
  • written informed
  • consent was obtained from the infant’s parents or legal
  • guardian

Exclusion criteria:

  • infants with a coagulopathy, sepsis, a vertebral column
  • malformation, or a neurological disease

 

N total at baseline:

Intervention: 25

Control: 25

 

Important prognostic factors2:

age ± SD at time of surgery; in weeks:

I: 6.0 ± 3.9

C: 6.7 ± 2.1

 

Post-conceptual age (weeks)

I: 46.1 ± 5.3

C: 48.5 ± 6.4

Birth weight (g)

I: 2045.7 ± 893.8

C: 2019.3 ± 914.2

Weight at surgery (g)

I: 2245.7 ± 753.6C: 2481.7 ± 1004.9

Surgery duration (min)

I: 100.4 ± 32.2

C: 110.6 ± 60.7

 

Sex:

Not reported

 

Groups comparable at baseline.

 

Combined spinal-epidural anesthesia

 

CSEA infants (N = 25) were infants in whom spinal anesthesia was induced by injecting preservative-free isobaric 0.5% bupivacaine solution (0.8 mg kg-1) by a spinal puncture that was done using a 25-G styletted needle at either the L3–4 or L4–5 space when the patient was in the lateral position. After the onset of spinal anesthesia, a 20-G epidural catheter (B. Braun Medical, Inc. Melsungen, Germany) was inserted through a 19-G Crawford needle through the sacrococcygeal membrane and advanced to the desired thoracic segments. The epidural catheter was then filled with Omnipaque 300 in order to confirm correct placement of its tip between the T5 and T10 spinal segments or to adjust the position of its tip. A test dose of 0.1 mL/ kg of 1% lidocaine with 1:200,000 epinephrine was then administered to exclude intravascular placement by observing any increases in heart rate of at least 20% above the baseline heart rate and/or changes in the ST-segment of the ECG. Thirty to forty minutes after the onset of spinal  anesthesia, 0.5 mL/kg of plain 0.25% bupivacaine was injected into the epidural catheter, and this injection was followed by a continuous infusion of plain 1%

bupivacaine at a rate of 0.2–0.3 mg/kg/h intra- and for 48 h post-operatively in the NICU.

The magnitude of the sensory and motor block was determined within 10 min of the spinal bupivacaine injection by observing the infant’s response to a 30-mA

tetanic stimulus which was delivered by a peripheral nerve stimulator (Innervator NS-252, Fisher & Paykel Healthcare Ltd, Auckland, New Zealand). Surgical anesthesia was established by the absence of startling, crying, limb flexion

withdrawal reflexes, and arching of the torso, and increases in blood pressure and heart or respiratory rates by more than 20% above baseline values. If the infant appeared fussy but not in pain, the infant was pacified with either a

50% glucose solution or incremental 0.05 mg kg-1 doses of intravenous midazolam up to a maximal dose of 0.2 mg/kg. The success of CSEA was defined as when (a) the lumbar puncture and access to the sacral canal were achieved within three attempts, (b) the epidural catheter was correctly placed between the T5 and T10 segments within three attempts of catheter re-insertion, and (c) the anesthesia was adequate for surgery and obviated the need for additional systemic analgesia. Whenever spinal anesthesia or insertion of the epidural catheter failed, CSEA was immediately switched to GA with endotracheal intubation and the infant was removed from the study.

General anesthesia including fentanyl

 

GA infants (N = 25) were infants whose anesthesia

was induced by intravenously administered propofol (2–4 mg kg-1) and fentanyl (2–4 lg kg-1), and whose endotracheal intubation was facilitated by rocuronium (0.5 mg kg-1). After endotracheal intubation and before

the start of surgery, the location of the endotracheal tube was confirmed by chest X-ray. Anesthesia was maintained by 0.5–1.5% of isoflurane in air/oxygen and intravenous fentanyl, as needed. The infants were ventilated by the nonrebreathing

technique in order to keep the end-tidal carbon

dioxide concentration in the expired air (ETCO2) between 30 and 45 mmHg. Neuromuscular blockade was reversed at the end of surgery using neostigmine and atropine. Full recovery from the neuromuscular blockade was confirmed by monitoring train-of-four stimulation and by observing the ability of the infants to sustain lifting of all limbs prior to extubation and to maintain appropriate respiratory function. Postoperative fentanyl was administered in the

NICU as a continuous infusion (2–5 lg kg-1 h-1) as needed as a function of the Crying Requires Oxygen Increased Vital Signs Expression Sleep (CRIES) score for measuring postoperative pain in neonates [9].

 

Length of follow-up:

8-day follow-up period

 

Loss-to-follow-up & incomplete outcome data:

Intervention: 2/25 (8%)

Control:  1/25 (4%)

 

Reasons not specified; methods described ‘Whenever spinal anesthesia or insertion of the epidural catheter failed, CSEA

was immediately switched to GA with endotracheal intubation and the infant was removed from the study.’

 

 

I: n=23

C: n=24

 

Postoperative pain

Not reported

 

Postoperative opioid consumption

Not reported

 

Length of stay

Not reported

 

Adverse events

Respiratory events

Total number of infants who had a cardiovascular adverse event

I: 3/23 (13)

C: 11/24 (44%)

 

Cardiovascular events

Total number of infants who had a cardiovascular adverse event

I: 11 (47.8)

C: 20 (80)

  Of which:

  Tachycardia

  I: 1 (4.3)

  C: 2 (8.3)

  Tachycardia and hypotension

  I: 3 (13)

  C: 3 (13)

  Tachycardia and hypertension

  I: 0 (0)

  C: 3 (13)

  Bradycardia

  I: 4 (17.4)

  C: 8 (33)

  Ventricular premature beats

  I: 3 (13.0)

  C: 4 (17)

 

Urinary retention

Not reported

Time to first oral feeding

Not reported

 

 

Gannam-Somri, 2020

Type of study:

RCT

 

Setting and country: single-center; Israel

 

Funding and conflicts of interest: “The authors have no conflict of interest.”; funding not  reported

neonates undergoing

elective gastrointestinal surgery.

 

Inclusion criteria:

  • Neonates who underwent elective gastrointestinal surgery, including duodenoduodeno-stomy or duodeno-jejunostomy for duodenal atresia, ileocaecal resection for intestinal volvulus, ileostomy or colostomy closure for congenital anorectal malformations, and corrective surgery for Hirschsprung disease.
  • All operations were performed by open approach (laparotomy).

 

Exclusion criteria:

  • vertebral column malformations,
  • neurological disease,
  • coagulopathy,
  • sepsis,
  • immune deficiency with or without leukopenia,
  • necrotising enterocolitis,
  • exploratory laparotomy or emergent intestinal surgery

 

N total at baseline:

Intervention: 28

Control: 30

 

Important prognostic factors2:

Age, median [range]: wks

I: 5.5 [0, 28]

C: 10 [0, 47

Sex:

Not reported

 

Gestational age

(wk)

I: 39.5 [30, 66]

C: 41 [28, 81]

Birth weight (g) I: 1934 ± 932

C: 2165 ± 873

Current weight (g) I: 2342 ± 874

C: 2889 ± 1176

Duration of surgery

(min) Range

I: 90 [45,180]

C: 90 [55,255]

 

Groups comparable at baseline.

Combined epidural‐general anaesthesia

 

In the CEGA group, after GA induction, epidural puncture was performed

through the sacrococcygeal membrane with a 19G Crawford needle, and a 20G epidural catheter (B. Braun Medical, Inc) was inserted through the caudal epidural needle. The catheter tip was located between T5 and T10 spinal segments. A portable epidurogram (Omnipaque® 300, Nycomed) was used to confirm correct placement of the epidural catheter after filling the catheter with 0.5 mL iohexol.

A test dose of 0.1 mL kg−1 of 1% lidocaine with 1:200 000 epinephrine was administered to rule out intravascular injection. A maximum of two attempts at epidural catheter placement was allowed.

Bupivacaine 0.25%, 0.5 mL kg−1 was injected through the epidural catheter, followed by a continuous infusion of 0.1% bupivacaine at a rate of 0.2 mg kg−1 h−1 for up to 48 hours post‐operatively.

 

 

 

 

General anaesthesia

 

GA was induced with propofol (2‐4 mg/kg) and fentanyl (2‐4 μg/kg).

Rocuronium bromide (0.5 mg/kg) was used to facilitate endotracheal

intubation and anaesthesia was maintained with 2%‐3% sevoflurane in an air/oxygen mixture, with the addition of intravenous fentanyl as required.

 

Following GA induction, a second intravenous catheter was

placed and infused with Ringer's lactate and 5% glucose solutions at a rate of 4 mL kg−1 h−1. Additional Ringer's lactate was administered, as guided by third‐space losses and intravascular fluid deficit. The intraoperative systolic and diastolic blood pressure (SBP and DBP respectively), as well as mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2), and body temperature of all patients were monitored continuously using an AS/3 Datex monitor (Engestrom®). All patients were mechanically ventilated with a peak

inspiratory pressure maintained between 18 and 30 cm H20, and to an end‐tidal CO2 (ETCO2) between 30 and 50 mmHg. Urine output was

measured every 30 minutes intraoperatively and post‐operatively.

Length of follow-up:

n.s.; at least 12

 

Loss-to-follow-up:

Intervention: 2/30; Epidural catheter insertion failed

Control: 0

 

Incomplete outcome data:

Intervention: 0

Control: 0

Postoperative pain

Not reported – score used to administer postoperative continuous infusion of fentanyl.

 

Anxiety

Not reported

 

Postoperative opioid consumption

24h

Not reported

Total

Median total fentanyl consumption (μg)

[range min, max]

I: 55 [40, 200]

C: 230 [60, 750]

P= <0.00

Other - Patients receiving opioids, n (%)

I: 6 (21%)

C: 30 (100%)

 

Length of stay

Not reported

 

Adverse events

respiratory depression?, pruritus, nausea, vomiting, epidural hematoma, epidural infection (abces), hypotension, nerve damage, accidental dural puncture, motor blockade, dizziness , Drowsiness, Redness insertion site catheter, failure (evt bij complicaties; bijvoorbeeld door dislokatie van de epiduraal)

n (%)

Surgical site infection

I: 3 (10.7)

C: 7 (23.3)

P= 0.2990

Urinary tract infection

I: 3 (10.7)

C: 4 (13.3)

P=1

Pneumonia

I: 3 (10.7)

C: 6 (20.0)

P=0.4720

Sepsis

I: 2 (7.14)

C: 5 (16.6)

P=0.4240

Fever of unknown origin

I: 2 (7.14)

C: 5 (16.6)

P=0.4240

Patients with ≥ 1 infection

I: 10 (35.7)

C: 18 (60.0)

P=0.038

 

Time to first oral feeding

post‐operative time to tolerance of full enteral nutrition; median [IQR] days

I: 4.0 days [IQR 1.0]

C: 8.0 days; [IQR 2.0 days]

P = .0001

“In the CEGA group, feeding was postponed for three patients for 3 hours due to abdominal distension. In the GA group, feeding was postponed for six patients for 2 hours, again due to abdominal distension.”

 

Bozkurt, 2003

Type of study:

RCT

 

Setting and country:

Single-center; Turkey

 

Funding and conflicts of interest:

“This work was

supported by the Research Fund of the University of

Istanbul.”

Conflicts not described

Inclusion criteria:

  • undergoing major genito-urinary or lower abdominal operations,
  • ranging in age from 1 to 15 years

 

Exclusion criteria:

  • taking opioids,
  • those under hormonal treatment
  • previous history of renal, cardiac or hepatic disease, epilepsy or asthma

 

N total at baseline:

Intervention:  25

Control: 25

 

Important prognostic factors2:

age ± SD years:

I: 6.7 ± 4.3 (range 1.5–14)

C: 6.4 ± 3.7 (range 1–15)

 

Sex:

I: 16/25; 64% M

C: 19/25; 76% M

Weight (kg)

I: 25 ± 14.1 (9–55)

C: 25.5 ± 13.7 (10–60)

Duration of

operation (min)

I: 145 ± 73.8 (50–320)

C: 138 ± 77.3 (60–420)

Operations

Lower abdominal

I: 9/25

C: 10/25

Genito-urinary

I: 16/25

C: 15/25

 

Groups comparable at baseline.

single dose of epidural morphine 0.1 mg/kg postinduction

 

 

[start with standard procedure, see control treatment]

The group EP patients were placed in a lateral position and the L3–4 epidural space found with loss of resistance to normal

saline. A 40 mm, 22-gauge spinal needle was used for

children aged less than 5 years and a 18-gauge Tuohy

needle (Perifix 401-Braun, Helsungen AG, Germany)

for the others, and an epidural catheter was placed. A single dose of morphine 0.1 mg/kg) was given epidurally. Bolus doses of morphine in prepared and labelled syringes were sent to the ward to be used

in case of pain.

 

Morphine infusion at 0.02 mg/kg/h following a bolus dose of 0.05 mg/kg at

induction

 

An intravenous catheter was inserted in the ward and unpremedicated

children were brought to the operating room following 8 h of fasting. General anaesthesia

was induced with thiopentone 5 mg/kg and muscle relaxation achieved with atracurium 0.5 mg/kg.

After intubation of the trachea, anaesthesia was

maintained with 50% O2 in N2O and 1% halothane.

For fluid maintenance Lactated Ringer’s solution was used, using the formula of 4-2-1 (4 ml/kg/h for

first 10 kg weight + 2 ml/kg/h for the next 10 kg

weight + 1 ml/kg/h for each kg thereafter) plus 2–

4-ml additional dose according to the tissue trauma ratio. All patients were mechanically ventilated with a tidal volume of 10 ml/kg) and rate adjusted to achieve PECO2 of 4.6–4.9 kPa (35–38 mmHg) and peak airway pressure of 20 cmH2O.

 

In the INF group morphine was infused at 0.02 mg/kg/h following a bolus dose of

0.05 mg/kg) and this was continued for 24 h.

Length of follow-up:

24 hours

 

Loss-to-follow-up & incomplete outcome data:

n.s.

 

 

Postoperative pain

FACES pain score; FACES pain scale (assessed by nurses as of five face drawing 0 = no hurt, 5 = hurt worst)

PACU / 0 hour; 6 hours;

Not reported

24 hours (Read from box plots in figure)

I: 2.0

C: 1.6

 

Other – FACES pain score

Read from box plots in figure

1 hour:

I: 1.9

C: 1.5

5 hours:

I: 2.0

C: 1.7

12 hours:

I: 1.9

C: 1.8

“None of the patients complained of pain that

required additional treatment during the follow-up

period. The median of pain scores was 2 at all times

in both groups. The pain score was never greater

than 3 in any patient (Figure 2).”

 

Postoperative opioid consumption

“In the postoperative period, none of the patients in EP group required the use of previously prepared morphine epidural doses. EP group received total of 0.1 mg/kg/day morphine, INF group delivered bolus dose of 0.05 mg/kg + total infusion dose 0.48 mg/kg/day morphine.”

 

Perova-Scharonova, 2021

Type of study:

randomized prospective study (concerning postoperative analgesia  (retrospectively divided in groups regarding abdominal hypertension (IAH) and abdominal

compartment syndrome (ACS)).

 

Setting and country:

Lviv Regional Pediatric

Clinical Hospital from February 2018 to February 2020; Ukraine

 

Funding and conflicts of interest: funding not reported; reported that no conflicts of interest exist.

 

Inclusion criteria:

  • age of 1–18 y
  • early postoperative stage after surgery for appendicular peritonitis, and absence of contraindications for intraabdominal pressure measurement throw urinary bladder catheterization

 

Exclusion criteria:

  • refusal of the patient or parents to participate in the study;
  • anamnesis of inflammatory bowel diseases, congenital pathology with malabsorption, and surgical interventions for intestinal resection, which may affect citrulline and

I-FABP levels;

the presence of contraindications to

intra-abdominal pressure measurement throw urinary bladder catheterization

 

Results from patients receiving postoperative epidural or opioids (not lidocaine) were included.

 

N total at baseline:

Intervention: 26

Control: 25

 

Important prognostic factors2:

Age in months,

mean (95% CI):

I: 115 (87–142)

C: 89 (65–113)

Sex:

I: 10/26; 3% M

C: 11/25; 44% M

Body mass, kg

I: 36 (28–44)

C: 24 (19–30)

Height, cm

I: 140 (127–153)

C: 125 (114–137)

 

Groups comparable at baseline.

Epidural anaesthesia

 

In children of the “EA” group (n = 26), epidural

catheter was placed throw puncture site in -12-L1

level using “loss of resistance” method and the

catheter was advanced up to -7--8 level; 0.25%

bupivacaine was administered with an initial bolus of 1 mg/kg and subsequent infusion of 0.4 mg/kg/year.

 

All children received intravenous paracetamol (60 mg/

kg/day) as multimodal analgesia regimen.

-e pain intensity was assessed at rest and during

movements using numerical rating scales (NRS) in children

above 7 years of age and Face, Legs, Activity, Cry, Consolability

(FLACC) scale in those below 7 years of age. In

cases of pain intensity ≥ 4 points, intravenous bolus of

morphine was administered in a dose of 100 mcg/kg.

 

 

 

Opioids

 

In patients of the “Opioids” group (n = 25), an intravenous infusion of morphine of 10 mcg/kg/h was administered.

 

All children received intravenous paracetamol (60 mg/

kg/day) as multimodal analgesia regimen.

-e pain intensity was assessed at rest and during

movements using numerical rating scales (NRS) in children

above 7 years of age and Face, Legs, Activity, Cry, Consolability

(FLACC) scale in those below 7 years of age. In

cases of pain intensity ≥ 4 points, intravenous bolus of

morphine was administered in a dose of 100 mcg/kg.

 

 

Length of follow-up:

n.s.

 

Loss-to-follow-up & incomplete outcome data:

n.s.

 

Postoperative pain

[Scale]

PACU / 0 hours:

6 hours:

24 hours

Not reported

Other: 3 days postoperatively (72h; Age ≥ 7 years: Numerical rating scales (NRS)

Age < 7 years: Face, Legs, Activity, Cry, Consolability

(FLACC), points)

NRS/FLACC at rest

I: 0 (0–0.5)

C: 1 (1–2)

NRS/FLACC during movements, points

I: 1 (0–1)

C: 2 (2–3)

 

Postoperative opioid consumption

Other - Morphine dose, mcg/kg/24 h

I: 0 (0–0)

C: 315.35 (187.2–510.3)

 

 

Mansfield, 2021

Type of study:

single-institution retrospective review

 

Setting and country:

 

Funding and conflicts of interest:

“This research was supported by the American Syrian Lebanese

Associated Charities (ALSAC/St. Jude Children’s Research

Hospital).”

“The authors have no conflicts of interest to disclose.”

Inclusion criteria:

  • all patients (children) undergoing thoracotomy or laparotomy
  • from July 2015 to January 2020
  • at our children’s oncology hospital.

 

Exclusion criteria:

  • chronic opioids or those who required

opioids within 1 week prior to surgery

  • hemodynamically unstable patients
  • complications that significantly altered their post-operative course (remained intubated > 24 h post-operatively or required additional surgical interventions for surgical complications).
  • Surgeries that were not for tumor resections

 

Results from patients undergoing laparotomy (not thoracotomy) were included.

 

N total at baseline:

Intervention: 151

Control: 35

 

Important prognostic factors2:

Age ± SD:

I: 6.7 (± 5.8) years

C: 8.8 (± 7.6) years

Sex:

n.s.

 

Groups comparable at baseline.

Epidural anesthesia

 

Epidural catheters in this study were placed after

the induction of general anesthesia but prior to incision. The choice of epidural infusate was left to the discretion of the attending anesthesiologist, but most commonly consisted of a local anesthetic and fentanyl.

 

 

 

No epidural anesthesia

 

intravenous patient-controlled analgesia (PCA), and other regional anesthetics

Length of follow-up:

n.s.

 

Loss-to-follow-up & Incomplete outcome data:

n.a.

 

 

Postoperative pain

  • Age 1 month–3 years: face, legs, activity, cry, and consolability (FLACC) scale
  • Age 3–7 years: Wong–Baker Faces Pain Rating Scale
  • Age > 7 years: 0–10 Numeric Pain Rating Scale

PACU / 0 hours:

I: 1.22 (± 0.99)

C: 1.75 (± 1.33)

6 hours:

Not reported

24 hours:

I: 1.87 (± 1.25)

C: 2.19 (± 0.95)

Other FU

48h:

I: 1.62 (± 1.13)

C: 1.66 (± 1.11)

72h:

I: 1.42 (± 1.19)

C: 1.38 (± 1.01)

 

Postoperative opioid consumption

24h (POD 1)

I: 0.33 (± 0.3)

C: 0.93 (± 1.53)

Also: POD 1, 2, 3

 

Length of stay

Median (IQR) days

I: 4 (4–6)

C: 5 (4–6)

 

Adverse events

Not reported separately for laparotomy patients

 

Urinary retention

Number of days with a urinary catheter; median IQR

I: 3 (3–4)

C: 6 (1–4)

 

Time to first oral feeding

Time to resumption of regular diet, days, median IQR

I: 4 (3–4)

C: 3 (2–5)

 

Martin, 2019

Type of study:

retrospective cohort study included

 

Setting and country: USA, single center; nov 2011-nov 2014

 

Funding and conflicts of interest:

“Funding for data management and statistical

analysis was provided by the Seattle

Children’s Hospital Faculty Research Support Award, Center for Clinical and

Translational Research.”

Reported tat no conflicts exist.

Inclusion criteria:

  • infants
  • underwent general anesthesia with or without an epidural for an abdominal procedure.
  • Exploratory laparotomy, ureteral reimplantation, or bladder exstrophy repair between November 2011 and November 2014.

 

Exclusion criteria:

  • Infants who were intubated prior to the

procedure

 

N total at baseline:

Intervention: 47

Control: 35

 

Important prognostic factors2:

Age,

mean(SD), median (IQR) days:

I: 101.2 (102.6), 62.0 (6.0, 177.0)

C: 45.3 (67.1), 5.0 (2.0, 55.0)

Weight, mean (SD)

I: 5.02 (2.38)

C: 3.75 (1.66)

Sex:

n.s.

 

Groups comparable at baseline.

 

Epidural anesthesia

 

Ropivacaine 0.2%, 0.1 up to 0.4 mg/kg/hr was used for all epidurals per institutional standard. The dose was titrated to effect per the inpatient pain service protocols. No additives were used because of concerns regarding the potential risk of apnea with both opiates and clonidine.

 

Intravenous opioids including morphine (M), fentanyl (F), and

hydromorphone (HM) were ordered as needed for postoperative pain

management per pain service and administered at the discretion of the bedside nurse.

 

 

No epidural anesthesia

 

Intravenous opioids including morphine (M), fentanyl (F), and

hydromorphone (HM) were ordered as needed for postoperative pain

management per pain service and administered at the discretion of

the bedside nurse.

Length of follow-up:

n.s.

 

Loss-to-follow-up & incomplete outcome data:

Thirteen patients (16%) were excluded from

the secondary analysis due to incomplete data on NPASS pain scores or use of another pain scale (ie, FLACC).”

 

Postoperative pain

postoperative pain and sedation scores; measured by the Neonatal Pain, Agitation and Sedation Scale (NPASS), NPASS assessments were

performed and recorded per standard of care by following hospital guidelines: every 4 hours by RN, as needed, or more frequently if  intervention was made.

PACU / 0 hours:

6 hours:

24 hours:

Not reported

 

Other:

“The proportion of patients with NPASS pain scores at or below 5 (indicative of adequate analgesia) 72 hours following the end of anesthesia was similar between the two groups (73% vs. 67%, P = 0.8). However, there were more patients with NPASS sedation scores <0 (indicative of sedation) for the non‐epidural group

(30%) compared to the epidural group (13%) and two patients in the non‐epidural group had extreme sedation with NPASS scores < −5. (Figure S1).“ (Figure cannot be read for absolute values)

 

Postoperative opioid consumption

Opioid administration in the first 24 postoperative hours, median [IQR]

I: 0.24 mg/kg [IQR 0.09‐0.44]

C: 0.34 mg/kg [IQR 0.11‐0.5]

 

Phelps, 2019

Type of study:

retrospective cohort study included

 

Setting and country:

Single-center; USA

 

Funding and conflicts of interest:

CoI not mentioned;

“The authors would like to acknowledge the support of the Surgical Outcomes Center for Kids of Monroe Carell, Jr. Children’s Hospital. JR Robinson receives salary and tuition support by the T15 LM007450 training grant from the NIH National Library of Medicine.”

Kasai portoenterostomy for Biliary atresia (BA)

 

Inclusion criteria:

  • records containing an ICD-9 diagnosis code of 751.61 or ICD-10 code of Q44.2 (i.e., atresia of bile ducts)
  • surgery at ≤1 year of age

 

Exclusion criteria:

  • attending pediatric surgeon’s operative report stated that a diagnosis other than BA was found at time of surgical exploration
  • if the patient did not undergo PE, as determined by the operative report

 

N total at baseline:

Intervention: 25

Control: 22

 

Important prognostic factors2:

Age at PE (days); median [IQR]

I: 56.0 [40.0, 64.0]

C: 63.5 [44.5, 73.8]

Weight at PE (kg), median [IQR]

I: 4.3 [3.6, 4.7]

C: 4.5 [3.7, 5.2]

Sex:

I: 9/25; 36% M

C: 15/22; 68% M

Extubated after surgery

I: 88% (22/25)

C: 59% (13/22)

 

Groups comparable at baseline? More males in control group (68% vs. 36%); more patients extubated after surgery in intervention group (88% vs. 59%)

Epidural anesthesia

 

 

 

 

No epidural anesthesia

 

 

Length of follow-up:

n.s.

 

Loss-to-follow-up:

n.s.

Incomplete outcome data:

n.s.

 

Postoperative pain

Face, Legs, Activity, Cry, Consolability (FLACC) scale;

0-10; median [IQR]

PACU / 0 hours:

Not reported

6 hours:

I: 0.5 [0, 2.0]

C: 1.7 [0.2, 3.5]

24 hours:

I: 0 [0, 2]

C: 1.8 [1, 3.8]

Other: all 6-hour intervals up to 96 hours post surgery

 

Postoperative opioid consumption

systemic opioid administration; median [IQR]; units of (mg IV morphine / kg body weight)

I: no systemic opioids

C:

0 – 6h: 0.12 [0.06, 0.24]

6 – 12h: 0.11 [0.05, 0.30]

12 – 18h: 0.10 [0.06, 0.17]

18 – 24h: 0.11 [0.05, 0.23]

 

Length of stay

Length of hospital stay after PE; days, median [IQR]

I: 6 [5, 7]

C: 8 [6.3, 11]

 

Adverse events

Epidural or other complications

Apnea and/or bradycardia

I: 5/25

C: 6/22

Epidural-related events

  • Requiring re-intubation following post-operative extubation: 0
  • Transfer to IC: 0

Technical complications associated with the catheters

  • Epidural failure: 1; due to kink Catheters migrated out: 4
  • Removed upon parental request: 1

Time to first oral feeding

Time to first oral feed;

days, median [IQR]

I: 3 [2, 4]

C: 3 [2, 3]

NB: To normalize opioid dosing for the most accurate comparisons, the following factors were used to convert opioids administered intravenously (IV) and by mouth (PO) to a common unit of milligrams of IV morphine per kilogram of body weight: 1 mg IV morphine = 0.1 (IV fentanyl, mcg) = 6.7 (IV hydromorphone, mg) = 0.5 (PO oxycodone, mg) = 0.05 (PO codeine, mg) = 0.33 (PO hydrocodone, mg) (9).

 

Relland, 2022

Type of study:

matched retrospective cohort study

 

Setting and country:

USA;

Cases were identified between April 2018 through December 2019

 

Funding and conflicts of interest:

Reported that no funding was present and that no conflicts of interest exist.

 

Inclusion criteria:

Regional treatment group:

  • Chronologic postnatal age ≤6 months
  • under- went open abdominal surgery
  • presence of a continuous 2-chloroprocaine infusion

Matched control group:

  • Chronologic postnatal age ≤6 months
  • under- went open abdominal surgery
  • underwent systemic therapies alone

 

Exclusion criteria:

  • patients with a significant congenital anomaly or injury that could obfuscate pain assessment
  • underwent another surgery within the previous two months.
  • opioid dependence, and/or sedation that could complicate pain scoring;
  • any patient who was being treated preoperatively with a continuous intravenous in- fusion of opioid(s) and/or benzodiazepine(s).

 

N total at baseline:

Intervention: 24

Control: 24

 

Important prognostic factors2:

age ± SD:

Gestational age, weeks at birth [95% CI]

I: 33.3 [30.0, 36.6]

C: 33.6 [30.4, 36.8]

 

Age on day of surgery, weeks [95% CI], Postnatal I: 10.8 [6.9, 14.7] weeks

C: 8.5 [4.3, 12.7] weeks

 

Sex:

I: 45.8% M

C: 66.7% M

 

Groups comparable at baseline.

Epidural anesthesia

 

All patients in Group R had an epidural catheter inserted via the sacral hiatus. Performed directly by or overseen by the pain service team, the catheter tip was threaded cephalad under ultrasound guidance to the vertebral level corresponding to the center of the surgical dermatomes involved, then tunneled subcutaneously from the primary insertion site to exit laterally.

 

 

 

 

 

No epidural anesthesia (systemic therapy only)

 

 

 

Length of follow-up:

5 days

 

Loss-to-follow-up:

Incomplete outcome data:

n.s.

 

Postoperative pain

NPASS or FLACC

PACU / 0 hours:

6 hours:

24 hours:

Not reported

Other:

“Median daily pain score was ≤2 in both cohorts on all five days of the study period, indicating adequate pain control in the NICU for both groups in the postoperative period.”

- pain scores only available in whisker box plots with P-value.

Postoperative opioid consumption

Average per patient postoperative cumulative opioid consumption over the entire study period

I: 3.2 mg/kg

C: 19.7 mg/kg

p < 0.002

 

Adverse events

Serious adverse events; not further specified

I: 0

C: 0

 

 

Warmann, 2014

Type of study:

retrospectively; pair-matched historical control group

 

Setting and country:

Medical University Hospital Tübingen; July 2008 and March 2012; Germany

 

Funding and conflicts of interest:

funding not reported; interests not reported

Inclusion criteria:

  • all patients undergoing resection of an abdominal tumor at our institution between July 2008 and March 2012
  • in which continuous epidural analgesia was performed via a preoperatively placed thoracic catheter.

 

Exclusion criteria:

 

 

N total at baseline:

Intervention: 40

Control: 40

 

Important prognostic factors2:

Age at surgery [months]

I: 55.8 (41.6-74.9)

C: 39.0 (28.8-52.8)

Gender (male/female)

I: 22/18

C: 27/17

Body weight [kg]

I: 19.3 (15.9-23.5)

C: 15.9 (13.7-18.6)

Height [cm]

I: 111.4 (102.7-120.9)

C: 102.4 (94.4-111.0)

 

Groups comparable at baseline

 

continuous epidural

analgesia

 

Epidural catheters were always placed using ultrasound guidance,

the tip of the catheter being in a thoracic position (Fig. 1) [16,17].

Depending on age and height of the patients, epidural catheters were

either placed in awake patients before while sitting upright or after initiation of mechanical ventilation with patients in a lateral  position.

Catheters were either placed via thoracic insertion or via sacral insertion according to the patients’ age. The epidural cavity was

punctured using the saline-mediated loss-of-resistance-method [18,19]. Before catheter removal epidural analgesia was discontinued for a sufficient period to verify that patients were manageable otherwise.

Furthermore, heparin was stopped before removal according to the guidelines of the German Society for Anaesthesiology and Intensive Care Medicine [20]. All patients with continuous epidural analgesia also received a permanent transurethral urinary catheter for the time the epidural catheter was in place.

 

In the study group the postoperative analgesic management consisted of continuous epidural administration of ropivacaine 0.2% plus sufentanil 0.4 μg/ml together with a fixed administration of oral

or i.v. paracetamol (45 mg/kg/d) and metamizole (45 mg/kg/d). In case of persistent pain there were further measures taken in consecutive cadence: pre-ponement of oral/i.v. medication, acceleration of the epidural flow rate, and application of an additional piritramide bolus (0.05 mg/kg).

no epidural analgesia

 

 

The pain management concept in the control group consisted of application of i.v or oral paracetamol (45 mg/kg/d), ibuprofen (30 mg/kg/d), and metamizole (4 mg/kg/d). Furthermore, piritramide was applied either as a continuous i.v. infusion (0.3–0.5 mg/kg/d) or as an i.v. bolus via patient (parent) controlled analgesia (PCA).

Children below 24 months of age received continuous i.v. morphine instead of piritramide (below 6 months of age: 0.24 mg/kg/d, 6–24 months: 1.2–2.4 mg/kg/d).

Length of follow-up:

n.s.

 

Loss-to-follow-up:

Incomplete outcome data:

n.s.

 

 

Postoperative pain

Mean Pain Score (PS)

PACU / 0 hours:

6 hours:

Not reported

24 hours:

Mean Pain Score (PS) 24 h after surgery

I: 2.90 (range 2.22–3.58)

C: 3.57 (2.94–4.20)

 

Other - mean pain score 72 h after surgery

I: 0.97 (0.47–1.48)

C: 1.65 (1.06–2.24)

 

Length of stay

Hospital stay [d] mean

I: 11.7 (95% CI 10.2 to 13.5)

C: 10.4 (95% CI 8.8 to 12.3)

Time on ICU [d]

I: 1.44 (0.99–2.00)

C: 0.89 (0.56–1.29)

 

Adverse events

“There was no catheter-related complication in the study group; no

bleeding, allergic reactions or neurological complications occurred.

Also, no infectious complication (meningitis, urinary tract infection or

others) occurred.”

 

Time to first oral feeding

Time to complete oral feeding [d] mean

I: 3.91 (95% CI 3.11–4.90)

C: 3.64 (95% CI 2.86–4.62)

 

 

Wilson, 2001

Type of study:

retrospective analysis

 

Setting and country:

The General Infirmary at Leeds, Leeds, UK

 

Funding and conflicts of interest: n.s.

Inclusion criteria:

  • patients presenting to the General Infirmary at Leeds
  • for Nissen fundoplication, for documented pathological gastro-oesophageal reflux
  • between January 1994 and November 1997

 

Exclusion criteria:

 

 

N total at baseline:

Intervention: 65

Control: 39

 

Important prognostic factors2:

Median, range

Age (months)

I: 27 ( 3 – 168)

C: 26 (1 - 223)

Weight (kg)

I: 10.6 ( 3.2 - 54.7)

C:  9.0 (2.7 - 25.7)

Male : female ratio

I: 34 : 31

C: 21 : 18

 

Groups comparable at baseline

 

Epidural

 

Postoperative

epidural analgesia was provided by insertion of a low thoracic epidural catheter after induction of anaesthesia. This was utilized for infusion of a bupivacaine/fentanyl

mixture (0.125%, 4 microg/ml) according to a standardized

protocol. A maximum infusion rate of 0.4 ml/kg/h was prescribed, depending on

hourly pain assessments.

Patient case notes were

 

 

Opioids

 

A continuous morphine infusion was provided via a dedicated intravenous line, and the rate adjusted (10±40 microg/kg/h) according to hourly pain assessments. In some individuals on long-term antispasmodics, a continuous midazolam

infusion was combined with the morphine.

Length of follow-up:

n.s.

 

Loss-to-follow-up:

n.s.

 

 

Postoperative pain

Not reported

 

Anxiety

Not reported

 

Postoperative opioid consumption

Not reported

 

Length of stay

Duration (mean, range) of

hospital stay in days

I: 8  (3 - 53)

C: 13 (3 - 53)

Days in ICU

I: mean 2.4 (range 1 – 7)

C: mean 7 (range 1 - 31)

 

Adverse events

No absolute values reported;

Episodes of hypotension,

I: 25%

C: 10% (non sign. Diff.)

 

 

Text regarding (serieous) adverse events:

 

Tables 4 and 5 detail the results of postoperative

outcome measures, including requirement for ICU and ventilation, in both the opioid and epidural infusion groups. Intraoperative problems were restricted to episodes of hypotension, 25% in the

epidural group, and 10% in the opioid group (non significant difference). Postoperative surgical

problems were pre-dominantly minor, related largely to problems with the gastrostomy (infection, displacement and leaks), and not requiring reoperation.

Only one patient, in the epidural group, required early reoperation following the development of an

internal hernia and consequent small bowel obstruction.

Major respiratory complications, principally

development of postoperative pneumonia, were more common in the opioid infusion group. One

patient in each group developed a pneumothorax, requiring insertion of a chest drain. Other problems

were mostly related to those of establishing feeding and maintaining fluid balance.”

                             

 

Risk of bias table for intervention studies (randomized controlled trials; based on Cochrane risk of bias tool and suggestions by the CLARITY Group at McMaster University)

Study reference

 

(first author, publication year)

Was the allocation sequence adequately generated?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

 

Were patients blinded?

 

Were healthcare providers blinded?

 

Were data collectors blinded?

 

Were outcome assessors blinded?

 

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

LOW

Some concerns

HIGH

 

Somri, 2011

Probably yes

 

Reason: “Fifty envelopes, 25 containing odd and 25

containing even numbers obtained from a computer-generated

table ..”

 

Probably yes

 

Reason: “Fifty envelopes, 25 containing odd and 25

containing even numbers obtained from a computer-generated table were prepared and sealed to either a GA or CSEA group.”

No information

 

 

Definitely yes

 

Reason: 2/25 and 1/25 lost to FU.

No information

 

Reason: no protocol available and trial not registered

Probably no

 

Reason: No indications; reported that no conflicts exist; funding not reported

Some concerns

 

Reason: No information about blinding procedures; no protocol or trial registration available

Gannam-Somri, 2020

Probably yes

 

Reason: “Sixty patients were randomized using a computer‐generated list

(www.randomization.com) to either”

No information

No information

Definitely yes

 

Reason: 2/30 and 0/30 lost to FU; statistical analysis was performed “per protocol.”

Probably yes

 

Reason: trial registered; NCT03056261; outcomes that were stated to be primary, are now mentioned as secondary

Probably no

 

Reason: No indications; reported that no conflicts exist; funding not reported

Some concerns

 

Reason: No information about concealment of randomization and blinding procedures; ranking of outcomes differ slightly from registered protocol

Bozkurt, 2003

No information

No information

No information

Definitely yes

 

Reason: numbers in results indicate that no patient was lost to FU

No information

 

Reason: no protocol available and trial not registered

Probably no

 

Reason: No indications; funding reported; conflicts not specified

Some concerns

 

Reason: No information about randomization, concealment of randomization and blinding procedures; no protocol or trial registration available

Perova-Sharonova, 2021

Probably yes

 

Reason: “using a random number generator (https://www.random.

org).”

No information

No information

Probably yes

 

Reason: numbers in results indicate that no patient was lost to FU; no flow chart of excluded patients

No information

 

Reason: no protocol available and trial not registered

Probably no

 

Reason: No indications; reported that no conflicts exist; funding not reported

Some concerns

 

Reason: No information about concealment of randomization and blinding procedures; no protocol or trial registration available

 

Risk of bias table for interventions studies (cohort studies based on risk of bias tool by the CLARITY Group at McMaster University) 

Author, year

Selection of participants

 

Was selection of exposed and non-exposed cohorts drawn from the same population?

 

Exposure

 

 

Can we be confident in the assessment of exposure?

 

 

 

Outcome of interest

 

Can we be confident that the outcome of interest was not present at start of study?

 

Confounding-assessment

 

Can we be confident in the assessment of confounding factors? 

Confounding-analysis

 

Did the study match exposed and unexposed for all variables that are associated with the outcome of interest or did the statistical analysis adjust for these confounding variables?

Assessment of outcome

 

Can we be confident in the assessment of outcome?

 

 

 

 

Follow up

 

 

Was the follow up of cohorts adequate? In particular, was outcome data complete or imputed?

Co-interventions

 

Were co-interventions similar between groups?

 

Overall Risk of bias

 

 

 

 

 

 

 

 

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Definitely yes, probably yes, probably no, definitely no

Low, Some concerns, High

Mansfield, 2021

Definitely yes

 

Reason:

“all patients undergoing thoracotomy or laparotomy

from July 2015 to January 2020 at our children’s oncology

hospital”

 

Definitely yes

 

Reason:

Retrospective comparison

Probably yes

 

Reason:

Most relevant outcome measure (pain) caused by surgery

No information

 

Definitely no

 

Reason:

Data was not corrected for possible confounders

Probably yes

 

Reason:

All patients undergoing the intervention / control condition were included

Probably yes

 

Reason:

Outcome data seems to be complete, not imputed

Definitely no

 

Reason:

“In the laparotomy

cohort, PCA was utilized in 25 patients (16.6%) with EA and 27 patients (77.1%, p < 0.001)  without.”

“Local anesthetic was injected locally around the wound or as an ultrasound-guided perineural injection (trans-versus abdominus block, intercostal block, or erector spinae block) for 27 laparotomy patients without EA (77.1%) [….] No patients in the EA cohort received additional local anesthetic outside the epidural infusion.”

High risk (all outcomes)

Martin, 2019

Definitely yes

 

Reason:

Included all ‘infants (<12 months) who had an exploratory

laparotomy, ureteral reimplantation, or bladder exstrophy repair between

November 2011 and November 2014’

Definitely yes

 

Reason:

Retrospective comparison

Probably yes

 

Reason:

Most relevant outcome measure (pain) caused by surgery

No information

 

Definitely no

 

Reason:

Data was not corrected for possible confounders

Probably yes

 

Reason:

All patients undergoing the intervention / control condition were included

Probably no

 

Reason:

“Thirteen patients (16%) were excluded from the secondary analysis due to incomplete data on NPASS pain scores or use of another pain scale (ie, FLACC).”

- unclear whether these patients were epidural or non-epidural patients

Definitely no

 

Reason:

Intraoperative use of fentanyl dosage and yes/no morphine use and intra-operative ET sevoflurane concentration differ between groups.

 

High risk (all outcomes)

Phelps, 2019

Definitely yes

 

Reason: “All records containing an ICD-9 diagnosis code of 751.61 or ICD-10 code of Q44.2 (i.e., atresia of bile ducts) at 1 year of age or younger were ascertained.”

Definitely yes

 

Reason:

Retrospective comparison

Probably yes

 

Reason:

Most relevant outcome measure (pain) caused by surgery

No information

 

Definitely no

 

Reason:

Data was not corrected for possible confounders

Probably yes

 

Reason:

All patients undergoing the intervention / control condition were included

Probably yes

 

Reason:

Outcome data seems to be complete, not imputed;

Number of patient results per 6-hours interval were averaged to create intervals scores (“Since pain scores were recorded at inconsistent time intervals, each individual patient’s pain scores were averaged over 6-hour intervals”)

Definitely no

 

Reason:

Time in room pre-procedure, total non-operative time in room, extubation after surgery, ICU days and length of hospital stay differ between groups.

 

High risk (all outcomes)

Relland, 2022

Definitely yes

 

Reason:

“Infants at chronologic postnatal age ≤6 months who under- went open abdominal surgery between April 2018 through to the end of December 2019 were included in this study”

Definitely yes

 

Reason:

Retrospective comparison

Probably yes

 

Reason:

Most relevant outcome measure (pain) caused by surgery

No information

 

Definitely no

 

Reason:

Data was not corrected for possible confounders

Probably yes

 

Reason:

All patients undergoing the intervention / control condition were included

Probably yes

 

Reason:

Outcome data seems to be complete, not imputed;

 

Definitely no

 

Reason:

Previous surgery count, surgery done emergently, differ between groups

High risk (all outcomes)

Warmann, 2014

Definitely yes

 

Reason: “we retrospectively evaluated all patients undergoing resection of an abdominal tumor at our institution

between July 2008 and March 2012 in which continuous epidural analgesia was performed via a preoperatively placed thoracic

catheter.”

Definitely yes

 

Reason:

Retrospective comparison

Probably yes

 

Reason:

Most relevant outcome measure (pain) caused by surgery

No information

 

Definitely no

 

Reason:

Data was not corrected for possible confounders

Probably yes

 

Reason:

All patients undergoing the intervention / control condition were included

 

Probably yes

 

Reason:

Outcome data seems to be complete, not imputed;

 

Definitely no

 

Reason: time of anesthetic induction, operation time in minutes, time on ICU differ between groups

 

High risk (all outcomes)

Wilson, 2001

Definitely yes

 

Reason: “Case notes from a consecutive series of patients

presenting to the General In®rmary at Leeds for Nissen  fundoplication, for documented pathological

gastro-esophageal reflux, between January 1994

and November 1997 …”

Definitely yes

 

Reason:

Retrospective comparison

Probably yes

 

Reason:

Most relevant outcome measure (pain) caused by surgery

No information

 

Definitely no

 

Reason:

Data was not corrected for possible confounders

Probably yes

 

Reason:

All patients undergoing the intervention / control condition were included.

 

Probably yes

 

Reason:

Outcome data seems to be complete, not imputed.

 

Probably yes

 

Reason: no major intra operative procedural differences reported

 

Some concerns (all outcomes)

 

Table of excluded studies

Reference

Reason for exclusion

 Solanki NM, Engineer SR, Vecham P. Comparison of epidural versus systemic analgesia for major surgeries in neonates and infants. J Clin Neonatol 2017;6:23-8. doi: 10.4103/jcn.JCN_66_16

n < 10 per arm

Singh AP, Lakshminrusimha S, Thompson ME. Regional analgesia in neonates undergoing thoracoabdominal surgeries: A pilot study. J Neonatal Perinatal Med. 2019;12(1):73-79. doi: 10.3233/NPM-1827. PMID: 30320598.

n < 10 per arm

Bozkurt P. The analgesic efficacy and neuroendocrine response in paediatric patients treated with two analgesic techniques: using morphine-epidural and patient-controlled analgesia. Paediatr Anaesth. 2002 Mar;12(3):248-54. doi: 10.1046/j.1460-9592.2002.00791.x. PMID: 11903939.

does not meet PICO (I, C)

Zhu X, Yang H, Qu M, Wang J, Fei J, Shi L. Application of Intravenous Anesthesia in Laparoscopic Hiatal Hernia Repair of Children. Contrast Media Mol Imaging. 2022 Jun 29;2022:5290813. doi: 10.1155/2022/5290813. PMID: 35845740; PMCID: PMC9259264.

does not meet PICO (I,C)

Baird R, Guilbault MP, Tessier R, Ansermino JM. A systematic review and meta-analysis of caudal blockade versus alternative analgesic strategies for pediatric inguinal hernia repair. J Pediatr Surg. 2013 May;48(5):1077-85. doi: 10.1016/j.jpedsurg.2013.02.030. PMID: 23701786.

does not meet PICO (P)

Aouad MT, Kanazi GE, Siddik-Sayyid SM, Gerges FJ, Rizk LB, Baraka AS. Preoperative caudal block prevents emergence agitation in children following sevoflurane anesthesia. Acta Anaesthesiol Scand. 2005 Mar;49(3):300-4. doi: 10.1111/j.1399-6576.2005.00642.x. PMID: 15752392.

does not meet PICO (P)

Balent E, Edwards M, Lustik M, Martin P. Caudal anesthesia with sedation for inguinal hernia repair in high risk neonates. J Pediatr Surg. 2014 Aug;49(8):1304-7. doi: 10.1016/j.jpedsurg.2013.11.005. Epub 2013 Nov 12. PMID: 25092095.

does not meet PICO (P)

Gurria J, Kuo P, Kao A, Christensen L, Holterman A. General endotracheal vs. non-endotracheal regional anesthesia for elective inguinal hernia surgery in very preterm neonates: A single institution experience. J Pediatr Surg. 2017 Jan;52(1):56-59. doi: 10.1016/j.jpedsurg.2016.10.019. Epub 2016 Oct 27. PMID: 27863823.

does not meet PICO (P)

Prys-Roberts C, Lerman J, Murat I, Taivainen T, Lopez T, Lejus C, Spahr-Schopfer I, Splinter W, Kirkham AJ. Comparison of remifentanil versus regional anaesthesia in children anaesthetised with isoflurane/nitrous oxide. International Remifentanil Paediatric Anaesthesia Study group. Anaesthesia. 2000 Sep;55(9):870-6. doi: 10.1046/j.1365-2044.2000.01607.x. PMID: 10947750.

does not meet PICO (I, C)

Tuncer S, Yosunkaya A, Reisli R, Tavlan A, CICekci F, Otelcioglu S. Effect of caudal block on stress responses in children. Pediatr Int. 2004 Feb;46(1):53-7. doi: 10.1111/j.1328-0867.2004.01839.x. PMID: 15043665.

does not meet PICO (I, C)

von Ungern-Sternberg BS, Regli A, Frei FJ, Hammer J, Schibler A, Erb TO. The effect of caudal block on functional residual capacity and ventilation homogeneity in healthy children. Anaesthesia. 2006 Aug;61(8):758-63. doi: 10.1111/j.1365-2044.2006.04720.x. PMID: 16867088.

does not meet PICO (I, C)

Lamoshi A, Lerman J, Dughayli J, Elberson V, Towle-Miller L, Wilding GE, Rothstein DH. Association of anesthesia type with prolonged postoperative intubation in neonates undergoing inguinal hernia repair. J Perinatol. 2021 Mar;41(3):571-576. doi: 10.1038/s41372-020-0703-4. Epub 2020 Jun 4. PMID: 32499596; PMCID: PMC7270742.

does not meet PICO (P)

Šabanović Adilović A, Rizvanović N, Adilović H, Ejubović M, Jakić A, Maksić H, Simić D. Caudal block with analgosedation - a superior anaesthesia technique for lower abdominal surgery in paediatric population. Med Glas (Zenica). 2019 Aug 1;16(2). doi: 10.17392/1017-19. Epub ahead of print. PMID: 31187612.

does not meet PICO (I, C)

Kumar A, Dogra N, Gupta A, Aggarwal S. Ultrasound-guided transversus abdominis plane block versus caudal block for postoperative analgesia in children undergoing inguinal hernia surgery: A comparative study. J Anaesthesiol Clin Pharmacol. 2020 Apr-Jun;36(2):172-176. doi: 10.4103/joacp.JOACP_100_19. PMID: 33013030 PMCID: PMC7480308 DOI: 10.4103/joacp.JOACP_100_19

does not meet PICO (I, C)

Ghobrial HZ, Shaker, EH. Effectiveness of multimodal preemptive analgesia in major pediatric abdominal cancer surgery. Anaesthesia, Pain & Intensive Care. VOL.23 - NO.3 - SEPTEMBER – 2019. doi: https://doi.org/10.35975/apic.v23i3.1132

does not meet PICO (I, C)

Tao B, Liu K, Wang D, Ding M, Yang N, Zhao P. Perioperative effects of caudal block on pediatric patients in laparoscopic upper urinary tract surgery: a randomized controlled trial. BMC Pediatr. 2019 Nov 11;19(1):427. doi: 10.1186/s12887-019-1812-0. PMID: 31711451; PMCID: PMC6844040.

does not meet PICO (I, C)

Lin Z, Fang Y, Yan L, Lin Y, Liu M, Zhang B, He Y, Shen Y, Wu D, Zhang L. General versus general anaesthesia combined with caudal block in laparoscopic-assisted Soave pull-through of Hirschsprung disease: a retrospective study. BMC Anesthesiol. 2021 Aug 30;21(1):209. doi: 10.1186/s12871-021-01431-5. PMID: 34461833; PMCID: PMC8404309.

does not meet PICO (I, C)

Opfermann P, Wiener C, Schmid W, Zadrazil M, Metzelder M, Kimberger O, Marhofer P. Epidural versus general anesthesia for open pyloromyotomy in infants: A retrospective observational study. Paediatr Anaesth. 2021 Apr;31(4):452-460. doi: 10.1111/pan.14114. Epub 2021 Jan 29. PMID: 33368903; PMCID: PMC8048494.

does not meet PICO (I, C)

Benka AU, Pandurov M, Galambos IF, Rakić G, Vrsajkov V, Drašković B. Efeitos do bloqueio peridural caudal em pacientes cirúrgicos pediátricos: estudo randomizado [Effects of caudal block in pediatric surgical patients: a randomized clinical trial]. Braz J Anesthesiol. 2020 Mar-Apr;70(2):97-103. doi: 10.1016/j.bjan.2019.12.003. Epub 2020 Feb 20. PMID: 32204919; PMCID: PMC9373225.

does not meet PICO (P)

Faasse MA, Lindgren BW, Frainey BT, Marcus CR, Szczodry DM, Glaser AP, Suresh S, Gong EM. Perioperative effects of caudal and transversus abdominis plane (TAP) blocks for children undergoing urologic robot-assisted laparoscopic surgery. J Pediatr Urol. 2015 Jun;11(3):121.e1-7. doi: 10.1016/j.jpurol.2014.10.010. Epub 2015 Apr 9. PMID: 25921701.

does not meet PICO (I)

Akinyemi OA, Soyannwo OA. Evaluation of the perioperative analgesic effects of caudal block for herniotomy in children at the University College Hospital Ibadan, Nigeria. Afr J Med Med Sci. 2013 Mar;42(1):73-9. PMID: 23909097.

does not meet PICO (P)

Bravenboer-Monster K, Keyzer-Dekker C, van Dijk M, Staals L, Leeuw T, Wijnen R. Efficacy of Epidural Analgesia after Laparotomy in Children. Eur J Pediatr Surg. 2019 Apr;29(2):209-214. doi: 10.1055/s-0038-1632372. Epub 2018 Feb 19. PMID: 29458228.

wrong study design

Golladay S, Hutter S, Koehn E, Hunt T, Gutta R,  Gerbasi F, Corpron C, Hagan A, Dell T, and Selley K. A Comparison of Caudal Block and Acetaminophen Preemptive Analgesia in Pediatric Peritoneoscopy. Pediatric Endosurgery & Innovative Techniques. 2004; Vol. 7, No. 2. Published Online:8 Jul 2004 doi: 10.1089/109264103766757907

does not meet PICO (P, I)

Golladay S, Hutter S, Koehn E, Hunt T, Gutta R, Gerbasi F, Corpron C, Hagan A, Dell T, and Selley K. Preemptive Analgesia for Pediatric Peritoneoscopy, Comparing Caudal Block and Acetaminophen. Pediatric Endosurgery & Innovative TechniquesVol. 6, No. 1 Full Reports. Published Online: 8 Jul 2004. doi: 10.1089/10926410252832384

does not meet PICO (P, I)

Post-operative analgesia in children: Caudal block with bupivacaine, rectal diclofenac and combination of both
July 2008Journal of Anaesthesiology Clinical Pharmacology 24(3):321-324
N. Gupta, Renu Wakhloo, A. Mehta, Dimple Wali, S. Gupta

does not meet PICO (I)

Schnabel A, Thyssen NM, Goeters C, Zheng H, Zahn PK, Van Aken H, Pogatzki-Zahn EM. Age- and procedure-specific differences of epidural analgesia in children--a database analysis. Pain Med. 2015 Mar;16(3):544-53. doi: 10.1111/pme.12633. Epub 2015 Jan 19. PMID: 25599577.

wrong study design

Patel A, Stasiowska M, Waheed U, Brett SJ, Patel PB. Poor analgesic efficacy of epidural analgesia in critical care patients after pancreaticoduodenectomy. Pancreas. 2014 Apr;43(3):373-9. doi: 10.1097/MPA.0000000000000031. PMID: 24622066.

does not meet PICO (P)

Autorisatiedatum en geldigheid

Laatst beoordeeld  : 17-12-2024

Laatst geautoriseerd  : 17-12-2024

Geplande herbeoordeling  : 17-12-2028

Initiatief en autorisatie

Initiatief:
  • Nederlandse Vereniging voor Anesthesiologie
Geautoriseerd door:
  • Nederlandse Orthopaedische Vereniging
  • Nederlandse Vereniging voor Anesthesiologie
  • Nederlandse Vereniging voor Heelkunde
  • Verpleegkundigen en Verzorgenden Nederland
  • Nederlandse Vereniging van Ziekenhuisapothekers
  • Stichting Kind en Ziekenhuis

Algemene gegevens

De ontwikkeling/herziening van deze richtlijn werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijn is in 2022 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor kinderen met postoperatieve pijn.

 

Werkgroep

Dr. L.M.E. (Lonneke) Staals, anesthesioloog, voorzitter, NVA

Dr. C.M.A. (Caroline) van den Bosch, anesthesioloog-pijnspecialist, NVA

Drs. A.W. (Alinde) Hindriks-Keegstra, anesthesioloog, NVA

Drs. G.A.J. (Geranne) Hopman, anesthesioloog, NVA

Drs. L.J.H. (Lea) van Wersch, anesthesioloog, NVA

Dr. C.M.G. (Claudia) Keyzer-Dekker, kinderchirurg, NVvH

Drs. F.L. (Femke) van Erp Taalman Kip, orthopedisch kinderchirurg, NOV

Dr. L.M.A. (Laurent) Favié, ziekenhuisapotheker, NVZA

J. (Jantine) Boerrigter-van Ginkel, verpleegkundig specialist kinderpijn, V&VN

S. (Sharine) van Rees-Florentina, recovery verpleegkundige, BRV

E.C. (Esen) Doganer en M. (Marjolein) Jager, beleidsmedewerker, Kind & Ziekenhuis

 

Klankbordgroep

Dr. L.M. (Léon) Putman, cardiothoracaal chirurg, NVT

R. (Remko) ter Riet, MSc, anesthesiemedewerker/physician assistant, NVAM

Drs. L.I.M. (Laura) Meltzer, KNO-arts, NVKNO

 

Met ondersteuning van

Dr. L.M.P. Wesselman, adviseur, Kennisinstituut van de Federatie Medisch Specialisten

I. van Dijk, junior adviseur, Kennisinstituut van de Federatie Medisch Specialisten

Belangenverklaringen

De Code ter voorkoming van oneigenlijke beïnvloeding door belangenverstrengeling is gevolgd. Alle werkgroepleden hebben schriftelijk verklaard of zij in de laatste drie jaar directe financiële belangen (betrekking bij een commercieel bedrijf, persoonlijke financiële belangen, onderzoeksfinanciering) of indirecte belangen (persoonlijke relaties, reputatiemanagement) hebben gehad. Gedurende de ontwikkeling of herziening van een module worden wijzigingen in belangen aan de voorzitter doorgegeven. De belangenverklaring wordt opnieuw bevestigd tijdens de commentaarfase.

Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten.

 

Werkgroeplid

Functie

Nevenfuncties

Gemelde belangen

Ondernomen actie

L.M.E. Staals (voorzitter)

Anesthesioloog

Sectorhoofd Kinder- en Obstetrische anesthesiologie

Universitair Docent

Erasmus MC Sophia Kinderziekenhuis, Rotterdam

Lid wetenschapcommissie Sectie Kinderanesthesiologie (NVA) (onbetaald)

Lid scientific forum ESAIC/Devices abd Technology (onbetaald)

Lid werkgroep Landelijke Kwaliteitsregistratie Amandeloperaties (NVKNO/NVA) (onbetaald)

MSD/ Merck: i.v.m. een clinical trial naar sugammadex bij kinderen: Consultant of Global Clinical Trial Operations in the Netherlands. Betaald (inkomsten gaan op onderzoekskostenplaats van de afdeling Anesthesiologie Erasmus MC Sophia). Dit onderzoek gaat over sugammadex (antagonist voor spierverslapping).

Klinisch onderzoek gedaan naar postoperatieve pijnstilling bij kinderen na buikchirurgie, d.m.v. wondcatheter met lokaal anestheticum (nog niet gepubliceerd, daarom niet meegenomen in search van de richtlijn). Er is geen belang bij het advies van de richtlijn.

Geen restricties

C.M.A. van den Bosch

Anesthesioloog - pijnspecialist Prinses Maxima Centrum

Geen

Geen

Geen restricties

A.W. Hindriks-Keegstra

Anesthesioloog UMC Utrecht

 

Geen

VR ter behandeling van postoperatieve pijn en angst bij kinderen.

Geen restricties. Extern gefinancierd onderzoek valt buiten bestek van de richtlijn

G.A.J. Hopman

Anesthesioloog, Radboud UMC, Nijmegen

Geen

Geen

Geen restricties

L.J.H. van Wersch

Anesthesioloog, Maasziekenhuis Pantein

Geen

Geen

Geen restricties

C.M.G. Keyzer-Dekker

Kinderchirurg, Erasmus MC Sophia.

Geen

Geen

Geen restricties

F.L. van Erp Taalman Kip

Orthopedisch kinderchirurg, Erasmus Medisch Centrum Rotterdam

-Docent Fontys Hogeschool Eindhoven, curriculum kinder- podotherapie

-Docent TNO Leiden, onderwijs Jeugdartsen,

- Trainer stichting Skills4Comfort

Geen

Geen restricties

L.M.A. Favié

Ziekenhuisapotheker Erasmus MC

Geen

Geen

Geen restricties

J.Boerrigter-van Ginkel

Verpleegkundig Specialist Kinderpijn, Wilhelmina Ziekenhuis Utrecht.

Geen

Geen

Geen restricties

S. van Rees-Florentina

Recovery verpleegkundige Flevoziekenhuis Almere
Pijnconsulent i.o. Flevoziekenhuis Almere

Bestuurslid BRV BRN Nederland

 

Geen

Geen restricties

E.C. Doganer

Stichting Kind&Ziekenhuis Junior Projectmanager/beleidsmedewerker

Geen

Geen

Geen restricties

M. Jager

Stichting Kind&Ziekenhuis Junior Projectmanager/beleidsmedewerker

Begeleider C bij Sherpa, betaald

Geen

Geen restricties

Klankbordgroeplid

Functie

Nevenfuncties

Gemelde belangen

Ondernomen actie

L.M. Putman

Congenitaal cardio-thoracaal chirurg, Leids Universitair Medisch Centrum & Amsterdam UMC, voltijd functie

Geen

Geen

Geen restricties

R. ter Riet

Anesthesiemedewerker/Physician Assistant Anesthesiologie/Pijngeneeskunde

Voorzitter NVAM, Voorzitter commissie (acute) pijn NVAM/V&VN

Geen

Geen restricties

L.I.M. Meltzer

Beatrix ziekenhuis Gorinchem, Rivas zorggroep

Geen

Geen

Geen restricties

 

Inbreng patiëntenperspectief

Er werd aandacht besteed aan het patiëntenperspectief door zitting van een afgevaardigde van de patiëntenvereniging (Stichting Kind & Ziekenhuis) in de werkgroep. De conceptrichtlijn is tevens voor commentaar voorgelegd aan de Patiëntenfederatie Nederland en Stichting Kind & Ziekenhuis en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.

 

Wkkgz & Kwalitatieve raming van mogelijke substantiële financiële gevolgen

Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz

Bij de richtlijn is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling zijn richtlijnmodules op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).

 

Uit de kwalitatieve raming blijkt dat er waarschijnlijk geen substantiële financiële gevolgen zijn, zie onderstaande tabel.

 

Module

Uitkomst raming

Toelichting

Module Epidurale analgesie bij abdominale chirurgie

Geen substantiële financiële gevolgen

Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (>40.000 patiënten), volgt ook uit de toetsing dat het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet en/of het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft, het geen toename in het aantal in te zetten voltijdsequivalenten aan zorgverleners betreft en het geen wijziging in het opleidingsniveau van zorgpersoneel betreft. Er worden daarom geen substantiële financiële gevolgen verwacht.

Werkwijze

AGREE

Deze richtlijnmodule is opgesteld conform de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).

 

Knelpuntenanalyse en uitgangsvragen

Tijdens de voorbereidende fase inventariseerde de werkgroep de knelpunten in de zorg voor kinderen met postoperatieve pijn. De werkgroep beoordeelde de aanbevelingen uit de eerdere richtlijn Postoperatieve pijn (NVA, 2013) op noodzaak tot revisie. Het raamwerk van de richtlijn voor volwassenen is ook kritisch bekeken als uitgangspunt. Op basis van de uitkomsten van de knelpuntenanalyse zijn door de werkgroep concept-uitgangsvragen opgesteld en definitief vastgesteld.

 

Uitkomstmaten

Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde de werkgroep welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. De werkgroep waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Tevens definieerde de werkgroep tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.

 

Methode literatuursamenvatting

Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder ‘Zoeken en selecteren’ onder Onderbouwing. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. Review Manager 5.4 werd gebruikt voor de statistische analyses. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.

 

Beoordelen van de kracht van het wetenschappelijke bewijs

De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (zie http://www.gradeworkinggroup.org/). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding).

GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).

 

GRADE

Definitie

Hoog

  • er is hoge zekerheid dat het ware effect van behandeling dicht bij het geschatte effect van behandeling ligt;
  • het is zeer onwaarschijnlijk dat de literatuurconclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Redelijk

  • er is redelijke zekerheid dat het ware effect van behandeling dicht bij het geschatte effect van behandeling ligt;
  • het is mogelijk dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Laag

  • er is lage zekerheid dat het ware effect van behandeling dicht bij het geschatte effect van behandeling ligt;
  • er is een reële kans dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Zeer laag

  • er is zeer lage zekerheid dat het ware effect van behandeling dicht bij het geschatte effect van behandeling ligt;
  • de literatuurconclusie is zeer onzeker.

 

Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in richtlijnen volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet één op één vergelijkbaar met het minimaal klinisch relevant verschil (Minimal Clinically Important Difference, MCID). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming met betrekking tot de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).

 

De beoordelingen van de literatuur en de conclusies zijn gedaan op basis van de GRADE systematiek. De werkgroep vindt het belangrijk om relevante beperkingen hiervan aan te geven.

 

De klinische vragen in deze richtlijn gaan veelal over een reductie van postoperatieve pijn en opioïdenconsumptie bij een individuele patiënt. Onderzoeken beschrijven de verschillen op groepsniveau, over studies met verschillende patiëntpopulaties en operaties heen. Opioïdenconsumptie is sterk afhankelijk van tijdstip, ingreep en ernst van de pijn. Door het werken met een absolute drempelwaarde in mg (i.p.v. een relatieve drempelwaarde in %) bereiken resultaten gemeten op vroege postoperatieve tijdstippen en in studies met ingrepen met relatief lage opioïdenconsumptie vaak niet de MCID. Daarbij komt ook dat de doelgroep van de huidige richtlijn enorm varieert in lengte en gewicht (van prematuur tot adolescent). Lengte en gewicht heeft grote invloed op het analgetische effect van een specifieke dosering, waardoor alleen kijken naar milligrammen niet volstaat. Waar mogelijk is ook de relatieve reductie in procenten beschreven.

De keuze van de MCID (absoluut verschil in pijnscore of opioïdenconsumptie) heeft een bepaalde mate van willekeurigheid en is niet absoluut te zien. Ook zijn de conclusies zo geformuleerd (en geven alleen beperkt antwoord op het effect op een individuele patiënt voor een specifieke ingreep). In de literatuur worden de eindpunten pijnscores en opioïdenconsumptie separaat van elkaar weer gegeven, suggererend dat deze onafhankelijk van elkaar zijn. Echter kunnen deze twee eindpunten niet onafhankelijk van elkaar beoordeeld worden; in ieder protocol is opgenomen dat pijn behandeld moet worden. Deze separate beoordeling geeft niet altijd een adequaat antwoord op de klinische vraag naar het analgetische effect van een interventie.

Daarnaast worden multimodale componenten als aparte interventies beoordeeld, echter de klinische vraag is naar de effectiviteit als bouwsteen van een multimodale werkwijze.

Voor doseringsadviezen wordt er verwezen naar betrouwbare bronnen, zoals het farmacotherapeutisch kompas of het kinderformularium.

 

Overwegingen (van bewijs naar aanbeveling)

Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje ‘Overwegingen’ en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision framework is een integraal onderdeel van de GRADE methodiek.

 

Formuleren van aanbevelingen

De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. De kracht van het wetenschappelijk bewijs en het gewicht dat door de werkgroep wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Conform de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. De werkgroep heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.

In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.

 

Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers

 

 

Sterke aanbeveling

Zwakke (conditionele) aanbeveling

Voor patiënten

De meeste patiënten zouden de aanbevolen interventie of aanpak kiezen en slechts een klein aantal niet.

Een aanzienlijk deel van de patiënten zouden de aanbevolen interventie of aanpak kiezen, maar veel patiënten ook niet.

Voor behandelaars

De meeste patiënten zouden de aanbevolen interventie of aanpak moeten ontvangen.

Er zijn meerdere geschikte interventies of aanpakken. De patiënt moet worden ondersteund bij de keuze voor de interventie of aanpak die het beste aansluit bij zijn of haar waarden en voorkeuren.

Voor beleidsmakers

De aanbevolen interventie of aanpak kan worden gezien als standaardbeleid.

Beleidsbepaling vereist uitvoerige discussie met betrokkenheid van veel stakeholders. Er is een grotere kans op lokale beleidsverschillen.

 

Organisatie van zorg

In de knelpuntenanalyse en bij de ontwikkeling van de richtlijn is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, mankracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in de module Organisatie van zorg.

 

Commentaar- en autorisatiefase

De conceptrichtlijn werd aan de betrokken (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd ter commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijn aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijn werd aan de deelnemende (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd voor autorisatie en door hen geautoriseerd dan wel geaccordeerd.

 

Literatuur

Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey. BMJ Open. 2017 Nov 16;7(11):e018593. doi: 10.1136/bmjopen-2017-018593. PubMed PMID: 29150475; PubMed Central PMCID: PMC5701989.

 

Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016 Jun 28;353:i2016. doi: 10.1136/bmj.i2016. PubMed PMID: 27353417.

 

Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089. doi: 10.1136/bmj.i2089. PubMed PMID: 27365494.

 

Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010 Dec 14;182(18):E839-42. doi: 10.1503/cmaj.090449. Epub 2010 Jul 5. Review. PubMed PMID: 20603348; PubMed Central PMCID: PMC3001530.

 

Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13. doi: 10.1016/j.jclinepi.2017.05.006. Epub 2017 May 18. PubMed PMID: 28529184; PubMed Central PMCID: PMC6542664.

 

Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwalitieit. http://richtlijnendatabase.nl/over_deze_site/over_richtlijnontwikkeling.html

 

Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.

 

Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.

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