- Open Access
Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study
© Maury et al.; licensee Springer 2012
Received: 26 November 2011
Accepted: 14 June 2012
Published: 14 June 2012
We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device.
We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin].
Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71–48.8; p < 0.001).
The administration of on-demand medication through tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.
During the past decade, there has been increasing recognition of the challenge posed by optimization of glucose management in the heterogeneous critically ill population [1–4] The method, speed and degree of glycaemic control, most importantly hypoglycaemia, are increasingly recognized and debated [5–7]. Hypoglycemia occurring during IIT has been associated with severity score, ICU length of stay , outcome , inotropic support  hemodialysis , and errors in administering insulin . We present a retrospective analysis of hypoglycemic events in patients receiving continuously infused insulin via a complex central venous catheter (CVC) infusion set. We discuss concerns about the potential for untoward bolus administration of insulin and a method to limit its occurrence.
This study was a retrospective analysis of the nursing charts of patients admitted to a 14-bed ICU affiliated with a 760-bed teaching hospital. We assessed the charts of all consecutive nondiabetic patients during a 6-month period (from 13th March to 13th September 2009) equipped with an arterial line who were receiving multiple (more than 2) intravenous therapies, including IIT through a double CVC. The Institutional Review Board of our hospital authorized this retrospective analysis. All patients or next of kin gave their consent for the data obtained during their ICU stay to be retrospectively analyzed.
The features of hypoglycemic events while blood glucose was stabilized were analyzed. Stabilized blood glucose was defined as an insulin regimen unmodified for at least 3 hours in a patient receiving continuous enteral or parenteral nutrition. Hypoglycemic events were defined as the occurrence, in a patient previously receiving 3 IU or more of intravenous insulin hourly, of arterial blood glucose ≤ 90 mg/dL, for which insulin was stopped. Mild hypoglycemic events were defined as the impossibility of restarting insulin therapy for 2 hours; moderate hypoglycemic events required discontinuation of insulin for at least 3 hours. Blood glucose was initially measured hourly and then every 4 hours when insulin infusion was unmodified for 4 hours. Arterial blood glucose was measured using an indwelling catheter inserted for hemodynamic monitoring with the use of a hand-held blood glucose meter (Accu-Chek Performa, Roche Diagnostics France, Meylan, France). We compared patients according to the tubing system used (conventional tubing system or multiport infusion device) and assessed the incidence of hypoglycemia associated with the tubing system used.
Continuous variables are expressed as median with quartile intervals and compared using the Mann–Whitney U test. Categorical variables are compared using the Chi-squared or Fisher’s exact test as appropriate. The densities of hypoglycemic events for 1,000 hours of IIT were compared using the rate ratio.
Patient characteristics according to the device used to administer medications through the distal lumen of the central venous catheter
Multiport infusion device
Sex ratio: M/F
Median age (yr)
Days on mechanical ventilation
ICU length of stay (days)
ICU mortality n (%)
Cumulative IIT duration (h)
IIT duration median range (h)
Mild hypoglycemic event
Moderate hypoglycemic event
Hypoglycemic event incidence for 1000 h of IIT
The analysis of the hypoglycemic events showed that their incidence was significantly decreased when the multiport infusion device was used (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval (CI), 2.71–48.8; p < 0.001; Table 1). Only one mild hypoglycemic event was observed when the multiport infusion device was used. No medication infusion was noted prior to this event.
In this study, compared with classic tubing, the multiport infusion device was associated with a huge reduction in hypoglycemic events, possibly because of its low dead space.
As recently suggested , when patients are given IIT, care should be taken to use appropriate methods to: 1) infuse insulin (syringe-driven pump on a central line),and 2) measure blood glucose (prefer arterial to capillary samples, use suitable measurement device). However, to our knowledge no study has assessed the putative role of infusion tubing. It also is intriguing to note that reports of large multicenter, randomized, controlled trials assessing the impact of IIT make no mention of the tubing system used [1–4, 12]. The present study suggests that for patients on IIT and receiving multiple medications through complex infusion tubing, blood glucose variations may occur after interventions involving the infusion tubing, in the absence of any change in insulin infusion rate.
When using complex tubing, bolus administration of medication (sedation adjustment, antibiotic therapy, diuretics) results in the delivery of all the solutes present between the site of administration and the tip of the catheter. In the present study, the measured volume of solutes delivered to the patient in case of bolus administration through the 5-way valve ramp was 12.5 mL.
Our study does, however, have several limitations. First, it was a single-center, nonrandomized, retrospective analysis and has to be considered as a preliminary study. Second, even though the impact of the device on glycaemic control was not implicitly assessed, nurses were asked to assess the new device’s use and acceptability. We cannot therefore exclude that, when using this new device, the nursing team provided a more intensive level of care to the patient, leading to a more adequate insulin delivery. Third, in contrast to the findings of recent studies [5–7], no severe hypoglycemia was observed in the present survey. This could be due in part to our less stringent blood glucose target levels compared with those of Van den Berghe et al. . Fourth, the threshold of 90 mg/dL is not a usual value used to define hypoglycemia during IIT and is neither pertinent nor useful because it has no clinical implication. In fact, we chose this value and its definition not to detect hypoglycemia but to detect glucose imbalance in a patient who was previously in a steady state. We sought to show that complex infusion tubing can modify the accuracy of medication delivery. Insulin discontinuation when blood glucose was below 90 mg/dL also could explain in part the low rate of hypoglycemia that we observed. We acknowledge that insulin interruption is not a practice adopted by all intensivists prescribing IIT worldwide, although it was part of the NICE-SUGAR protocol . Fifth, the shorter median duration of IIT in the group of patients equipped with the multiport device could in part explain the difference in the incidence of hypoglycemic events. As a matter of fact, the duration of IIT has been associated with an increased incidence of hypoglycemia . However, this duration difference seems unlikely to be responsible for the observed in incidence difference of hypoglycemic events.
The use of a multiport infusion device with a limited dead space is associated with a lower incidence of hypoglycemic events. This is probably related to the fact that flushing of the tube contents is avoided with the multiport infusion device. Physicians should be aware of this phenomenon, which deserves further investigation.
- Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx , Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R: Intensive insulin therapy in critically ill patients. N Engl J Med 2001, 345: 1359–1367. 10.1056/NEJMoa011300PubMedView ArticleGoogle Scholar
- Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaerts H, Bouillon R: Intensive insulin therapy in the medical ICU. N Engl J Med 2006, 6: 49–61.Google Scholar
- The NICE-SUGAR Study Investigators: Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009, 360: 1283–1297.View ArticleGoogle Scholar
- Preiser JC, Devos P, Ruiz-Santan S, Mélot C, Annane D, Groeneveld J, Iapichino G, Leverve X, Nitenberg G, Singer P, Werneraman J, Joannidis M, Stecher A, Chiolero R: A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 2009, 35: 1738–1748. 10.1007/s00134-009-1585-2PubMedView ArticleGoogle Scholar
- Marik PE, Preiser JC: Toward understanding tight glycemic control in the ICU: a systematic review and metaanalysis. Chest 2010, 137: 544–551. 10.1378/chest.09-1737PubMedView ArticleGoogle Scholar
- Egi M, Bellomo R, Stachowski E, French CJ, Hart GK, Taori G, Hegarty C, Bailey M: Hypoglycemia and outcome in critically ill patients. Mayo Clin Proc 2010, 85: 217–224. 10.4065/mcp.2009.0394PubMed CentralPubMedView ArticleGoogle Scholar
- Vriesendorp TM, van Santen S, DeVries JH, de Jonge E, Rosendaal FR, Schultz MJ, Hoekstra JB: Predisposing factors for hypoglycemia in the intensive care unit. Crit Care Med 2006, 34: 96–101. 10.1097/01.CCM.0000194536.89694.06PubMedView ArticleGoogle Scholar
- Krinsley JS, Schultz MJ, Spronk PE, van Braam Houckgeest F, van der Sluijs JP, Melot C, Preiser JC: Mild hypoglycemia is strongly associated with increased intensive care unit length of stay. Ann Intensive Care 2011, 1: 49. 10.1186/2110-5820-1-49PubMed CentralPubMedView ArticleGoogle Scholar
- Arabi Y, Tamim H, Rishu A: Hypoglycemia with intensive insulin therapy in critically ill patients: predisposing factors and associations with mortality. Crit Care Med 2009, 37: 2536–2544. 10.1097/CCM.0b013e3181a381adPubMedView ArticleGoogle Scholar
- Garrouste-Orgeas M, Timsit JF, Vesin A, Schwebel C, Arnodo P, Lefrant JY, Souweine B, Tabah A, Charpentier J, Gontier O, Fieux F, Mourvillier B, Troche G, Reignier J, Dumay MF, Azoulay E, Regnier B, Carlet J, Soufir L, on behalf of the OUTCOMEREA Study group: Selected medical errors in the intensive care unit. Am J Respir Crit Care Med 2010, 181: 134–142. 10.1164/rccm.200812-1820OCPubMedView ArticleGoogle Scholar
- Hermanides J, Bosman RJ, Vriesdendorp TM, Dotsch R, Rosendaal FR, Zandstra DF, Hoekstra JB, Devries JH: Hypoglycemia is associated with intensive care unit mortality. Crit Care Med 2010, 38: 1430–1434. 10.1097/CCM.0b013e3181de562cPubMedView ArticleGoogle Scholar
- Brunkhorst F, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Shafer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K, for the german Competence Network Sepsis (Sepnet): Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358: 125–139. 10.1056/NEJMoa070716PubMedView ArticleGoogle Scholar
- Van den Berghe G, Schetz M, Vlasselaers D, Hermans G, Wilmer A, Bouillon R, Mesotten D: Intensive insulin therapy in critically Ill patients: NICE-SUGAR or Leuven blood glucose target? J Clin Endocrinol Metab 2009, 94: 3163–3170. 10.1210/jc.2009-0663PubMedView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.