Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

González-Michaca 2000

Type of study: randomized, controlled clinical trial

Setting: Instituto

Nacional de Ciencias Médicas y Nutrición Salvador

Zubirán (INCMNSZ)

Country: Mexico

Source of funding:?

Inclusion criteria:

Elective major surgery under general anesthesia or

spinal blockade

non-insulin-dependent diabetes mellitus (NIDDM).

Exclusion criteria:

patients with infections

(fever

37.9

C and/or leukocytosis

11,000/mm3),

hepatic damage, renal damage (serum creatinine

1.9 mg/dL),

morbid obesity (body mass index [BMI]

40), malnutrition

(serum albumin

to oral nutrition, parenteral nutrition requirement, -exclusive

use of human insulin, allergy and/or resistance to bovine insulin,

steroid ingestion, or refusal of patient or physician to

participate.

Statistical analysis included calculation of the arithmetic

N=

N= 19 subcutane insulin, 18 iv insuline

Mean age ± SD:

62.26 +/- 11.2 60.77 +/- 10.8

Sex: % M

37 en 39

Other important characteristics:

Control group:

N= 25

Mean age ± SD:

66.08 ± 13.2

Sex: % M

52

Other important characteristics:

Groups comparable at baseline?

Controlegroep ouder en langer dm hoewel niet significant.

Describe intervention (treatment/procedure/test

Algorithm sc administration of insulin or

Algorithm iv administration of insulin

Describe  control (treatment/procedure/test):

Routine management: insulin administration under no predetermined algorithm

Endpoint of follow-up:

They were followed for 48 h after surgery

For how many participants were no complete outcome data available?

-

Intervention group:

N (%): -

Control group:

N (%):-

Reasons for incomplete outcome data described?

-

Significant differences between groups?

Outcome measures and effect size (include 95%CI and p-value if available):

Results for

both experimental algorithms were similar except for the IV group that required less insulin

per hour compared to SC (0.64 vs. 0.34 U/h; p=0.0003).

The RM control group

showed poor control in all capillary glucose measurements (194.9+/- 26.8 mg/dL) compared

with the two experimental algorithms (SC 129.9 +/- 21) ; (IV 131.6 +/- 20.4) (p <0.05). More hyperglycemia events appeared in the RM group (p=

0.016). Only one hypoglycemia

event occurred in the IV group.

Non-concurrent control group

Hemmerling 2001

Type of study:

Prospective, double-blind randomized trial.

Setting:

University medical center

Country:

Canada.

Source of funding:

-

Inclusion criteria:

insulin-treated type

2 diabetic patients undergoing elective surgery of an

estimated time of more than 60 minutes

Exclusion criteria:

Patients with diabetic ketoacidosis during the perioperative

period and patients with impaired renal function

(creatinine concentration . 120 mmoL L-1) or impaired

hepatic function (based on routine liver function tests)

were excluded from the study.

N= ?

Intervention group:

Groups A and C (n 5 12 each) were treated with continuous modified glucoseinsulin-

potassium (GIK) infusion,

Mean age ± SD:

A: 64 +/- 11

C: 74 +/- 14

Sex: M /F

A: 6/6

C: 8/4

Other important characteristics:

Control group B and D:

treated with intermittent

IV insulin injections when glucose exceeded 12

mmoL L-1.

Mean age ± SD:

Sex: M /F

B: 5/7

D: 7/5

Other important characteristics:

Groups comparable at baseline? ja

Describe intervention (treatment/procedure/test):

Groups A and C (n 5 12 each) were treated with continuous modified glucoseinsulin-

potassium (GIK) infusion,

Describe  control (treatment/procedure/test):

Control group B and D:

treated with intermittent

IV insulin injections when glucose exceeded 12

mmoL L-1.

Mean age ± SD:

Endpoint of follow-up:

Glucose and potassium levels were measured every 15 minutes and 30

minutes during surgery and up to 4 hours post-surgery.

Plasma levels of lactate, cortisol,

glycerol, and free fatty acids were measured in arterial samples after intubation (S1), after

extubation (S2), and 4 hours after surgery

For how many participants were no complete outcome data available? -

Intervention group:

N (%): -

Control group:

N (%): -

Reasons for incomplete outcome data described?

-

Significant differences between groups?

-

Outcome measures and effect size (include 95%CI and p-value if available):

There was no significant difference in the time course

of plasma glucose levels during and after surgery among

the four groups

There was no significant difference

among the four groups concerning preoperative

glycemic control

Kang 2009

Type of study:

RCT

Setting:

?

Country:

South

Korea

Source of funding:

-

Inclusion criteria:

insulin-treated type 2 diabetic

patients undergoing elective surgery of an estimated time

of more than 120 min under general anaesthesia.

Exclusion criteria:

Patients with diabetic ketoacidosis

during the perioperative period, patients with impaired

renal function (creatinine concentration >1.4mgdl[1]1) or

impaired hepatic function (on the basis of routine liver

function tests) and patients with hypoglycaemic episode

in the hospital were excluded from the study.

N= ?

Intervention group:

insulin glargine,

n=15

Sex: % M

?

Other important characteristics:

Control group:

GIK, n¼15

Mean age ± SD:

66.08 ± 13.2

Sex:

?

Other important characteristics:

Groups comparable at baseline?

GIK groep ouder, niet significant.

Describe intervention (treatment/procedure/test):

In the insulin glargine

group, insulin glargine was administered by subcutaneous injection using an Optipen (Sanofi-Aventis) at 5 a.m. in consideration of the onset time of the drug, and

5% dextrose solution was started to titrate according to blood glucose levels at 5 p.m. (Table 1). Considering the surgical stress, the dose of insulin glargine was titrated by two-thirds of the total daily insulin dose required.

Describe  control (treatment/procedure/test):

In the GIK group, the continuous

GIK regimen [1000 ml 5% glucose+16 units of

short-acting insulin (Humulin)_20mmol KCl] was

started at 100 ml h[1]1 at 5 a.m.

Endpoint of follow-up:

During surgery, blood glucose levels were checked every

30 min from intubation to extubation and every 1 h up to

4 h after surgery

For how many participants were no complete outcome data available?

-

Intervention group:

N (%): 7 (14%)

Control group:

N (%):  0

Reasons for incomplete outcome data described?

Dropped out after surgery and were switched to CII regimen because degree of blood-glucoese control was unacceptable.

Significant differences between groups?

Yes.

Outcome measures and effect size (include 95%CI and p-value if available):

Li 2006

Type of study:

prospective, randomized, controlled study

Setting:

Department of Surgery, Mackay Memorial

Hospital and Mackay Junior

College of Nursing, Taipei

Country:

Taiwan

Source of funding: ?

Inclusion criteria:

diabetes mellitus who

were to undergo CABG for the 1st time.

Exclusion criteria:

?

N= ?

Intervention group:

N= 15

Mean age ± SD:

63.

Sex: % M

60.8%)

Other important characteristics:

Control group:

N= 42

Mean age ± SD:

63.7

Sex: % M

64.3

Other important characteristics:

Groups comparable at baseline?

Describe intervention (treatment/procedure/test):

Continuous Insulin Infusion (CII) Group. The CII

protocol (see Appendix) used in this group was modified

from the Portland protocol.11 Insulin was initiated

and the dosage titrated according to the results of glucose

testing to maintain the blood glucose between the

desired target levels.

Describe  control (treatment/procedure/test):

Patients in

the GGI group received subcutaneous insulin injections

(Humulin® R, Eli Lilly and Company; Indianapolis,

Ind) every 2 hours in an attempt to maintain blood

glucose levels between 150 and 200 mg/dL. The dose

of insulin was adjusted on the basis of each patient’s

response to the previous insulin injection.

When 2 consecutive measurements showed that the

target glucose level was attained, the frequency of GGI

injections was decreased to once every 4 hours. When

the patients began eating, the frequency of injections

was changed to 4 times per day (before every meal and

at bedtime). Given continuing stability in glucose-level

readings, the patient’s usual preoperative glucose-control

regimen was resumed 5 days after the operation.

Endpoint of follow-up:

For how many participants were no complete outcome data available?

7 patients in the GGI group dropped

out of the study after surgery and were switched to the

CII regimen because their personal surgeon considered

their degree of blood-glucose control to be unacceptable.

These 7 were excluded from our analysis.

Two CII patients (3.9%) and 1 GGI patient

(2.4%) died (

Intervention group:

N : 2

Control group:

N : 8

Reasons for incomplete outcome data described?

Significant differences between groups?

Outcome measures and effect size (include 95%CI and p-value if available):

The mean level on the day of

operation was 248.5 mg/dL (CII) versus 233.7 mg/dL

(GGI) (P=0.214).

In the CII group, blood glucose levels of less than 200 mg/dL were attained in 33 of 51 patients (65%), compared with only 12 of 42 patients (29%) in the GGI group (P <0.001).

The morning glucose levels

were significantly lower in the CII group (200.2 mg/dL

vs 231.4 mg/dL, P=0.046). A blood-glucose reading

of less than 200 mg/dL on the 1st postoperative day

was associated with better control during subsequent

days (Table IV), and the range of glucose change was

narrower.

The

time required to attain desirable glucose control was sig- nificantly shorter in the CII group (21.4 vs 30.5 hr,

P=0.013).

Umpierrez 2011

Type of study:

prospective, randomized, controlled study

Setting:

community teaching

hospital, a

tertiary referral academic institution and

a government healthcare teaching

hospital

Country:

US

Source of funding: ?

Inclusion criteria:

Adult patients admitted

to undergo general elective or emergency

surgery and not expected to require ICU

admission were eligible for inclusion. We

enrolled patients with a blood glucose

(BG) level between 140 mg/dL and 400

mg/dL who had a history of diabetes for

more than 3 months, aged 18–80 years

old, treated with diet alone, any combination

of oral antidiabetic agents, or lowdose

insulin therapy at a daily dose

#0.4 units/kg before admission.

Exclusion criteria:

Exclusion

criteria included hyperglycemia

without a known history of diabetes, cardiac

surgery, clinically relevant hepatic

disease or impaired renal function (serum

creatinine $ 3.0 mg/dL), history of diabetic

ketoacidosis (21), pregnancy, and

any mental condition rendering the subject

unable to give informed consent.

Intervention group:

N= 104

Mean age ± SD:

58 +/- 12

Sex: M/F

54/50

Other important characteristics:

Control group:

N= 107

Mean age ± SD:

57 +/- 10

Sex: M/F

53/54

Other important characteristics:

Groups comparable at baseline?

Describe intervention (treatment/procedure/test):

Patients treated with basalbolus

therapy were started at a total daily

dose (TDD) of 0.5 units/kg divided half

as insulin glargine once daily and the

other half as insulin glulisine given before

meals. If a patient was not able to eat, insulin glargine was given but insulin glulisine was

held until meals were resumed.

Describe  control (treatment/procedure/test):

Patients

randomized to SSI received regular insulin

four times daily for BG .140 mg/dL. The

doses of insulin were adjusted according

to a prespecified protocol (Supplementary

Table 1). For subjects receiving SSI, if the

mean daily BG level was .240 mg/dL,

or if three consecutive values were

.240 mg/dL on the maximal sliding

scale dose, patients were switched to

basal-bolus regimen starting at a TDD of

0.5 units/kg.

Endpoint of follow-up:

Glucose values:

For how many participants were no complete outcome data available?

23 patients.

Outcome measures and effect size (include 95%CI and p-value if available):

The mean daily glucose concentration after the 1st day of basal-bolus insulin and SSI was 145 +/-32 mg/dL and 172 +/-47 mg/dL, respectively (P , 0.01). Glucose readings <,140

mg/dL were recorded in 55% of patients in basal-bolus and 31% in the SSI group (P < 0.001).

Glucose <70 mg/dL was reported in 23.1%of patients in the basal-bolus group and 4.7%in the SSI group (P<0.001), but there were no significant differences in the frequency of BG ,40 mg/dL between groups (P = 0.057).

Hagelberg 2008

Type of study:

prospective, randomized, controlled study

Setting:

Karolinska Institute,

Country:

Stockholm, Sweden

Source of funding: ?

Inclusion criteria:

Forty-eight patients undergoing primary CABG

were studied after permission from the local ethics

committee and informed, signed consent. Only

patients with diabetes mellitus or impaired glucose

intolerance detected during the preoperative workup

were included.

Exclusion criteria:

Exclusion criteria were renal failure, known

diabetes and other endocrinological diseases. Patients

were randomised (sealed envelope method) to

two groups with different protocols for treating

post-operative hyperglycaemia (Lantus and Actrapid)

on the surgical wards after release from the

ICU.

N= ?

Intervention group:

N= 21

Mean age ± SD:

64.+/- 9.1

Sex: %F

14

Other important characteristics:

Control group:

N= 22

Mean age ± SD:

64.9 +/- 10.4

Sex: %F

18

Other important characteristics:

Groups comparable at baseline: BMI higher in control group

Describe intervention (treatment/procedure/test):

Group Lantus. Patients received 0.5 E/kg glargine

insulin sc (Lantus† Sanofi-Aventis AB, Sweden) at

the start of surgery. On the morning of Postoperative

Day 1 (POD-1) while still in the ICU,

patients receive 0.250.3 E/kg Lantus insulin sc

depending on insulin requirements after surgery,

the P-glu values at 6 o’clock and 8 o’clock.

On the mornings of POD’s 2-4, Lantus is given at

8 o’clock with dose adjusted according to the 03 and

06 o’clock fasting P-glu values with the target

interval of 4.57 mmol/l. Only Lantus insulin is

given, but if pre-prandial P-glu]10 mmol/l rescue

Actrapid is given with dose as below for Actrapid

group.

Describe  control (treatment/procedure/test):

Group Actrapid. Patients received regular insulin sc

(Actrapid†, NovoNordisk AB, Sweden) by ward

nurses according to a protocol when their preprandial

P-glu exceeds 10 mmol/l. The dose Actrapid

given was 8 international units (IU) if P-glu]10

mmol/l, 10 IU if P-glu]12 mmol/l, 12 IU if P-glu]

14 mmol/l and 14 IU if P-glu]16 mmol/l.

Endpoint of follow-up:

Study period 14 days after surgery.

For how many participants were no complete outcome data available?

three

patients in the Lantus group and two in the Actrapid

group were dropped from the study. Two patients

required extended intensive care and/or extended

glucose drip, one returned to intensive care, and one

patient developed a stroke on POD- 2 and received

extended glucose drip.

Intervention group:

N :

Control group:

N : 

Reasons for incomplete outcome data described?

Significant differences between groups?

Outcome measures and effect size (include 95%CI and p-value if available):

Primary endpoint was percent of pre- and post-prandial P-glu values within Target Intervals: Pre-prandial P-glu: 4.5-7 mmol/l; postprandial P-glu: 4.5-9 mmol/l. Study period 1-4 days after surgery. Tissue glucose was also measured continuously. More than twice as many P-glu values were within Target Interval for Lantus patients as compared with Actrapid patients (pB0.001). One of 504 timed measurements wasB4 mmol/l. Area under the curve for glucose 7 mmol/l was reduced by 61% by Lantus (pB0.001).

Diez 1991

Type of study:

RCT

Setting:

Country:

Spain

Source of funding: unknown

Inclusion criteria:

Non-insulin dependent type 2 diabetes patients admitted to hospital for programmed surgical operations under general anaesthesia

Exclusion criteria:

Not stated

N= 14

Control group:

N= 7

Mean age ± SD:

67.8 ± 11.0

Sex: M /F

2/5

Other important characteristics:

Intervention group:

N= 7

Mean age ± SD:

62.6 ± 5.6

Sex: M /F

¾

Other important characteristics:

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Group II intensified treatment: mixture of 5% glucose (125 ml/h) and potassium chloride (3.75 mmol/h) by i. v.

Describe  control (treatment/procedure/test):

Group I; mixture of 5% glucose (125 ml/h) and potassium chloride (3.75 mmol/h) and rapid-acting insulin (1 to 4.5 U/h)

Endpoint of follow-up:  4 days after surgery

For how many participants were no complete outcome data available?

Intervention group:

N (%): not stated

Control group:

N (%):

not stated

Reasons for incomplete outcome data described?

not stated

Significant differences between groups?

not stated

Outcome measures and effect size (include 95%CI and p-value if available):

At day 2, 3 and 4 glycemic profiles were similar in both groups.

Hypoglycemia (glucose level < 2.8 mmol/l): group 1 à 1 episode per 28 patient-days and group 2 à 1 episode per 9.3 patient-days.

Schroeder 2012

Type of study:

Prospective RCT

Setting:

Department of orthopaedic surgery

Country:

Israel

Source of funding:

Not stated

Inclusion criteria:

All patients’ previously diagnosed diabetes or suffering from recurrent hypoglycaemia (two or more measurements of blood glucose levels > 180 mg/dL) who were admitted to the orthopaedic surgery department via the ER.

Exclusion criteria:

Not stated

N=

Intervention group: N=70

Mean age ± SD:

Not stated

Sex: M /F

1:1

Other important characteristics:

Control group:

N=71

Sex: M /F

1:1

Mean age ± SD:

Not stated

Other important characteristics:

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Glycaemic control intervention

Describe  control (treatment/procedure/test):

Standard sliding scale:

Endpoint of follow-up:

7 days after surgery

For how many participants were no complete outcome data available?

Intervention group:

N (%): 0

Control group:

N (%): 0

Reasons for incomplete outcome data described?

Not applicable

Significant differences between groups?

Not applicable

Outcome measures and effect size (include 95%CI and p-value if available):

Mean blood glucose levels:

I: 161.48 ± 3.8 mg/dL

C: 175.29 ± 2.3 mg/dL (p < 0.005)

Severe hypoglycaemic events significant lower (P<0.05) in intervention group. 

Study reference

(first author, year of publication)

There was adequate concealment of allocation

(yes/no/unclear)

Participants receiving care were kept ‘blind’ to treatment allocation

(yes/no/unclear)

Care providers were kept ‘blind’ to treatment allocation

(yes/no/unclear)

Outcome assessors were kept ‘blind’ to participants’ exposure to the intervention

(yes/no/unclear)

 Use of unvalidated or  intermediate

outcomes

(yes/no/unclear)

Selective outcome reporting on basis of the results

(yes/no/unclear)

Loss to follow-up/incomplete outcome data described and acceptable

(yes/no/unclear)

Analysis by

intention to treat

(yes/no/unclear)

Other limitations

(yes/no/unclear)

Gonzalez-Michaca 2002

No

No

No

No

No

No

No

No

Non-concurrent control group

Hemmerling 2001

No

No

No

No

No

No

No

No

Kang 2009

No

No

No

No

No

No

No

No

Li 2006

No

No

No

No

No

No

No, selective loss to follow up in intervention group. 

No

Umpierrez 2011

Yes

No

No

No

No

No

Yes

No

Hagelberg 2008

Yes

No

No

No

No

No

No

No

Diez 1991

No

No

No

No

No

No

No

No

Schroeder 2012

Unclear

No

No

No

No

No

Yes

No