Objectives: Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest.
Design: Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as “Cerebral Performance Category.”
Setting: Thirty-six sites in Europe and Australia.
Patients: All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial.
Interventions: Targeted temperature management at 33°C or 36°C.
Measurements and Main Results: Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3–5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03–1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group.
Conclusion: Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.
1Department of Intensive and Perioperative Care, Skåne University Hospital, Lund, Sweden.
2Department of Clinical Sciences, Lund University, Lund, Sweden.
3Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom.
4Department of Anaesthesia and Intensive Care, Intensive Care Unit, Helsingborg Hospital, Sweden.
5Cardiothoracic Intensive Care Unit, St. George’s Hospital NHS Foundation Trust, London, United Kingdom.
6Department of Intensive Care, Royal Bournemouth Hospital, Bournemouth, United Kingdom.
7Department of Neurology, Skåne University Hospital, Lund, Sweden.
8Department of Critical Care, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom.
9Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
10Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
11Department of Cardiology and Angiology, General University Hospital in Prague, Prague, Czech Republic.
12Department of Intensive Care, Royal Berkshire Hospital, Reading, United Kingdom.
*See also p. 1415.
The complete list of board members for the TTM-Trial Investiators are: Anders Aneman (Australia), Tobias Cronberg (Sweden), David Erlinge (Sweden), Hans Friberg (Sweden), Yvan Gasche (Switzerland), Christian Hassager (Denmark), Jan Hovdenes (Norway), Janneke Horn (The Netherlands), Jesper Kjaergaard (Denmark), Michael Kuiper (The Netherlands), Niklas Nielsen (Sweden), Thomas Pellis (Italy), Pascal Stammet (Luxemburg), Michael Wanscher (Denmark), Jørn Wetterslev (Denmark), and Matt P. Wise (United Kingdom).
Some of the data in this article has been presented at the 5th International Hypothermia and Temperature Management Symposium in Edinburgh (2014) and at the 2015 annual meeting of the European Society of Intensive Care Medicine in Berlin.
Dr. Borgquist had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Borgquist and Friberg acquired, analyzed, and interpreted the data. Dr. Borgquist drafted the article. Drs. Wise, Nielsen, Al-Subaie, Cranshaw, Cronberg, Glover, Hassager, Kjaergaard, Kuiper, Smid, Walden, and Friberg reviewed and revised the article for important intellectual content.
Dr. Wise was funded 40% whole time equivalent during the study by a National Institute for Social Care and Health Research Academic Health Science Collaboration Clinical Research Fellowship; received travel costs from the British Thoracic Society, Intensive Care Society, Scottish Intensive Care Society, Orion; royalties from Wiley Publishing; honorarium for lecturing at educational meeting Fisher & Paykel, and Merck; serves on the advisory board for Kalobius Pharmaceuticals, Bard; editor BMJ Open Respiratory Research. Dr. Wise disclosed other support from Teleflex, Kimberly Clark, Healthcare 21 and Qualitech Healthcare—gift of endotracheal tubes for investigator led study. Dr. Nielsen received speaker’s honorarium from Bard International. His institution received grant support from the Swedish Heart and Lung foundation, Arbetsmarknadens Försäkringsaktiebolag Insurance Foundation, Swedish Research Council, and from Regional and Governmental funds within the Swedish Health Care system. Dr. Glover received fees for consulting and travel costs from Bard Medical. Dr. Friberg received lecture fees from Bard Medical and is a scientific advisor for QuickCool. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: oborgquist@gmail.com
