Abstract
Purpose
A safe and effective insulin infusion algorithm that achieves rigorous intraoperative glycemic control in noncardiac surgery has yet to be formally characterized and evaluated. We therefore report the validation of the DeLit Trial insulin infusion algorithm.
Methods
Patients scheduled for major noncardiac surgery were randomized to a target intraoperative blood glucose concentration of 4.4-6.1 mmoL·L−1 (80-110 mg·dL−1) intensive group or 10-11.1 mmoL·L−1 (180-200 mg·dL−1) conventional group. Glucose was managed with a dynamic intravenous insulin infusion algorithm. We compared the randomized groups on glucose time-weighted average (TWA), proportion of time spent within target, number of severe (< 2.2 mmoL·L−1 or < 40 mg·dL−1) or moderate (< 2.8 mmoL·L−1or < 50 mg·dL−1) hypoglycemic episodes, and within-patient variability in glucose concentrations expressed as standard deviation from the patient mean.
Results
One hundred eighty-seven patients were assigned to intensive glucose control, and 177 patients were assigned to conventional glucose control. Median (lower quartile value [Q1], upper quartile value [Q3]) of intraoperative TWA for the intensive vs conventional groups was 6 [5.6, 6.7] mmoL·L−1 vs 7.7 [6.9, 9.2] mmoL·L−1, respectively; P < 0.001. The intensive group spent 49% (29, 71) of the time within target, substantially more time than the conventional group spent either within the intensive target or within its own target (both P < 0.001). The intensive group had slightly lower within-patient glucose variability than the conventional group (0.9 [0.7, 1.3] mmoL·L−1 vs 1.3 [0.8, 1.8] mmoL·L−1, respectively; P < 0.001). Three patients had moderate hypoglycemia (intensive group), but none experienced severe episodes.
Conclusion
Tight intraoperative glucose control in noncardiac surgery can be maintained successfully without serious hypoglycemic episodes. (ClinicalTrials.gov number, NCT00433251).
Résumé
Objectif
Nous ne disposons pas encore d’un algorithme de perfusion d’insuline formellement caractérisé et évalué, qui soit à la fois sécuritaire et efficace, et qui permette de maintenir un contrôle glycémique peropératoire rigoureux en chirurgie non cardiaque. C’est pourquoi nous rapportons la validation de notre algorithme de perfusion de l’insuline.
Méthode
Des patients devant subir une chirurgie non cardiaque majeure ont été randomisés à une concentration glycémique peropératoire cible de 4,4-6,1 mmoL·L−1 (80-110 mg·dL−1) dans le groupe intensif ou à une concentration de 10-11,1 mmoL·L−1 (180-200 mg·dL−1) dans le groupe conventionnel. La glycémie a été contrôlée à l’aide d’un algorithme dynamique de perfusion intraveineuse d’insuline. Nous avons comparé les groupes randomisés en matière de moyenne pondérée dans le temps, de la proportion de temps passé à la concentration cible, du nombre d’épisodes d’hypoglycémie grave (< 2,2 mmoL·L−1 ou < 40 mg·dL−1) ou modérée (< 2,8 mmoL·L−1 ou < 50 mg·dL−1), ainsi que de la variabilité chez un même patient des concentrations glycémiques, exprimée en tant qu’écart type de la moyenne du patient.
Résultats
Cent quatre-vingt-sept patients ont été attribués au groupe contrôle glycémique intensif, et 177 au groupe contrôle glycémique conventionnel. La médiane (valeur du quartile inférieur [Q1], valeur du quartile supérieur [Q3]) de la moyenne pondérée dans le temps pour les groupes intensif vs conventionnel était de 6 (5,6, 6,7) mmoL·L−1 vs 7,7 (6,9, 9,2), respectivement; P < 0,001. Le groupe intensif a passé 49 % (29, 71) du temps dans la zone cible, soit considérablement plus de temps que le groupe conventionnel n’a passé dans la zone cible intensive ou dans sa propre zone cible (tous deux P < 0,001). Le groupe intensif a présenté une variabilité chez un même patient légèrement plus basse que le groupe conventionnel (0,9 [0,7, 1,3] mmoL·L−1 vs 1,3 [0,8, 1,8] mmoL·L−1, respectivement; P < 0,001). Trois patients ont présenté une hypoglycémie modérée (groupe intensif), mais aucun patient n’a manifesté d’épisode grave.
Conclusion
Un contrôle glycémique peropératoire rigoureux peut être maintenu en chirurgie non cardiaque sans épisode hypoglycémique grave. (Numéro de ClinicalTrials.gov, NCT00433251).
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Acknowledgement
The DeLiT Trial is supported by Aspect Medical (Newton, MA) and the Cleveland Clinic Research Project Committee. Aspect Medical was purchased recently by Covidien (Dublin, Ireland). None of the authors has a personal financial interest in this research.
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Appendices
Appendix 1: Intensive glucose control
Target: 4.4-6.1 mmoL·L−1 (80-110 mg·dL−1)
Initiation of insulin infusion
Blood Glucose mmoL.L−1 (mg.dL−1) | Intravenous Bolus | Start Infusion At |
|---|---|---|
6.1-7.2 (110-130) | 2 units | 2 units/hr, recheck in 1/2 hr |
7.3-8.3 (131-150) | 2 units | 3 units/hr, recheck in 1/2 hr |
8.4-11.1 (151-200) | 3 units | 3 units/hr, recheck in 1/2 hr |
11.2-13.9 (201-250) | 5 units | 4 units/hr, recheck in 1/2 hr |
13.94-16.7 (251-300) | 5 units | 6 units/hr, recheck in 1/2 hr |
>16.7 (300) | 7 units | 8 units/hr, recheck in 1/2 hr |
Infusion adjustment
Blood Glucose mmoL·L−1 (mg·dL−1) | Decreasing Blood Glucose (↓ by more than 1.1 mmoL·L−1(20 mg·dL−1) | Stable Blood Glucose (No more than 1.1 mmoL·L−1(20 mg·dL−1) ↓ or ↑) | Increasing Blood Glucose (↑ by more than 1.1 mmoL·L−1(20 mg·dL−1) | Recheck in |
|---|---|---|---|---|
3.3 (< 60) | Hold infusion; give 50% dextrose 10-50 mL. | Hold infusion; give 50% dextrose 10-50 mL. | Hold infusion; give 50% dextrose 10-50 mL. | Immediately |
Notify staff anesthesiologist | Notify staff anesthesiologist | Notify staff anesthesiologist | ||
3.4-4.4 (61-80) | Stop infusion | Stop infusion | Continue same rate | ½ hr |
4.5-6.1 (81-110) | Decrease rate by 50% | Continue same rate | Increase rate by 25% | ½ hr |
Max. increase = 10 units/hr | ||||
6.2-7.2 (111-130) | Decrease rate by 25% | Bolus 2 units iv and maintain the current rate | Bolus 2 units iv and increase rate by 25% | ½ hr |
Max. increase = 10 units/hr | ||||
7.3-8.3 (131-150) | Decrease rate by 25% | Bolus 2 units iv and increase rate by 50% | Bolus 2 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
8.4-11.1 (151-200) | Continue same rate | Bolus 3 units iv and increase rate by 50% | Bolus 3 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | New rate = current rate x 2 | |||
Max. increase = 10 units/hr | ||||
11.2-13.9 (201-250) | Bolus 3 units iv and continue same rate | Bolus 3 units iv and increase rate by 50% | Bolus 4 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
13.94-16.7 (251-300) | Bolus 4 units iv and continue same rate | Bolus 4 units iv and increase rate by 50% | Bolus 5 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
16.72-19.4 (301-350) | Bolus 5 units iv and continue same rate | Bolus 5 units iv and increase rate by 50% | Bolus 7 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
19.5-22.2 (351-400) | Bolus 7 units iv and continue same rate | Bolus 7units iv and increase rate by 50% | Bolus 7 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
> 22.2 (400) | Bolus 8 units iv and continue same rate Notify staff anesthesiologist | Bolus 8 units iv and increase rate by 50% | Bolus 10 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
Notify staff anesthesiologist | Notify staff anesthesiologist |
1. Blood glucose may be checked via arterial blood gas analyzer or bedside glucose monitor;
2. The above are guidelines only. Insulin infusions may need modification for certain individuals based on clinical judgement and different clinical situations;
3. Round infusion rates to nearest 0.5 mL·hr−1.
Appendix 2: Conventional glucose control
Target: 10-11.1 mmoL·L−1 (180-200 mg·dL−1)
Initiation of insulin infusion
Blood Glucose mmoL·L−1 (mg·dL−1) | Intravenous Bolus | Start Infusion At |
|---|---|---|
11.9-13.9 (215-250) | 2 units | 2 units/hr, recheck in 1/2 hr |
13.94-16.7 (251-300) | 3 units | 3 units/hr, recheck in 1/2 hr |
16.72-19.4 (301-350) | 4 units | 4 units/hr, recheck in 1/2 hr |
19.5-22.2 (351-400) | 6 units | 6 units/hr, recheck in 1/2 hr |
>22.2 (400) | 7 units | 8 units/hr, recheck in 1/2 hr |
Infusion adjustment
Blood Glucose mmoL·L−1 (mg·dL−1) | Decreasing Blood Glucose (↓ by more than 1.7 mmoL·L−1(30 mg·dL−1) | Stable Blood Glucose (No more than 1.7 mmoL·L−1(30 mg·dL−1) ↓ or ↑) | Increasing Blood Glucose (↑ by more than 1.7 mmoL·L−1(mg·dL−1) | Recheck in |
|---|---|---|---|---|
< 3.3 (60) | Hold infusion; give 50% dextrose 10-50 mL. Notify staff anesthesiologist | Hold infusion; give 50% dextrose 10-50 mL. | Hold infusion; give 50% dextrose 10-50 mL. | Immediately |
Notify staff anesthesiologist | Notify staff anesthesiologist | |||
3.4-8.3 (61-150) | Stop infusion | Stop infusion | Stop infusion | ½ hr |
8.4-10.0 (151-180) | Stop infusion | Decrease infusion by 50% | Continue same rate increase rate by 25% | ½ hr |
10.1-11.9 (181-215) | Stop infusion | Continue same rate | Max. increase = 10 units/hr | ½ hr |
12-12.8 (216-230) | Decrease rate by 25% | Bolus 2 units iv and increase rate by 25% | Bolus 2 units iv and increase rate by 25% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
12.83-13.9 (231-250) | Continue same rate | Bolus 3 units iv and increase rate by 50% | Bolus 3 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | New rate = current rate x 2 | |||
Max. increase = 10 units/hr | ||||
13.94-16.7 (251-300) | Bolus 3 units iv and continue same rate | Bolus 3 units iv and increase rate by 50% | Bolus 4 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
16.72-19.4 (301-350) | Bolus 4 units iv and continue same rate | Bolus 4 units iv and increase rate by 50% | Bolus 5 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
19.5-22.2 (351-400) | Bolus 5 units iv and continue same rate | Bolus 5 units iv and increase rate by 50% | Bolus 7 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
22.3-25 (401-450) | Bolus 7 units iv and continue same rate | Bolus 7 units iv and increase rate by 50% | Bolus 7 units iv and increase rate by 50% | ½ hr |
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
>25 (450) | Bolus 8 units iv and continue same rate | Bolus 8 units iv and increase rate by 50% | Bolus 10 units iv and increase rate by 50% | ½ hr |
Notify staff anesthesiologist | ||||
Max. increase = 10 units/hr | Max. increase = 10 units/hr | |||
Notify staff anesthesiologist | Notify staff anesthesiologist |
1. Blood glucose may be checked via arterial blood gas analyzer or bedside glucose monitor;
2. The above are guidelines only. Insulin infusions may need modification for certain individuals based on clinical judgement and different clinical situations;
3. Round infusion rates to nearest 0.5 mL·hr−1;
4. Blood glucose may be checked at longer intervals (e.g., 60 min) if there was no intervention in the term of an insulin bolus or change of infusion rate and if the concentration has been stable for two readings.
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Abdelmalak, B., Maheshwari, A., Kovaci, B. et al. Validation of the DeLiT Trial intravenous insulin infusion algorithm for intraoperative glucose control in noncardiac surgery: a randomized controlled trial. Can J Anesth/J Can Anesth 58, 606–616 (2011). https://doi.org/10.1007/s12630-011-9509-3
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DOI: https://doi.org/10.1007/s12630-011-9509-3