Nutrition delivery, workload and performance in a model-based ICU glycaemic control system.

BACKGROUND AND OBJECTIVE: Hyperglycaemia is commonplace in the adult intensive care unit (ICU), and has been associated with increased morbidity and mortality. Effective glycaemic control (GC) can reduce morbidity and mortality, but has proven difficult. STAR is a model-based GC protocol that uniquely maintains normoglycaemia by changing both insulin and nutrition interventions, and has been proven effective in controlling blood glucose (BG) in the ICU. However, most ICU GC protocols only change insulin interventions, making the variable nutrition aspect of STAR less clinically desirable. This paper compares the performance of STAR modulating only insulin, with three simpler alternative nutrition protocols in clinically evaluated virtual trials. METHODS: Alternative nutrition protocols are fixed nutrition rate (100% caloric goal), CB (Cahill et al. best) stepped nutrition rate (60%, 80% and 100% caloric goal for the first 3 days of GC, and 100% thereafter) and SLQ (STAR lower quartile) stepped nutrition rate (65%, 75% and 85% caloric goal for the first 3 days of GC, and 85% thereafter). Each nutrition protocol is simulated with the STAR insulin protocol on a 221 patient virtual cohort, and GC performance, safety and total intervention workload are assessed. RESULTS: All alternative nutrition protocols considerably reduced total intervention workload (14.6-19.8%) due to reduced numbers of nutrition changes. However, only the stepped nutrition protocols achieved similar GC performance to the current variable nutrition protocol. Of the two stepped nutrition protocols, the SLQ nutrition protocol also improved GC safety, almost halving the number of severe hypoglycaemic cases (5 vs. 9, P = 0.42). CONCLUSIONS: Overall, the SLQ nutrition protocol was the best alternative to the current variable nutrition protocol, but either stepped nutrition protocol could be adapted by STAR to reduce workload and make it more clinically acceptable, while maintaining its proven performance and safety.

Interpretation of Retrospective BG Measurements.

BACKGROUND: This study investigates blood glucose (BG) measurement interpolation techniques to represent intermediate BG dynamics, and the effect resampling of retrospective BG data has on key glycemic control (GC) performance results. GC protocols in the ICU have varying BG measurement intervals ranging from 0.5 to 4 hours. Sparse data pose problems, particularly in comparing GC performance or model fitting, and thus interpolation is required. METHODS: Retrospective data from SPRINT in Christchurch Hospital Intensive Care Unit (ICU) (2005-2007) were used to analyze several interpolation techniques. Piecewise linear, spline, and cubic interpolation functions, which force interpolation through measured data, as well as 1st and 2nd Order B-spline basis functions, are used to identify the interpolated trace. Dense data were thinned to increase sparsity and obtain measurements (Hidden Measurements) for comparison after interpolation. Performance is assessed based on error in capturing hidden measurements. Finally, the effect of minutely versus hourly sampling of the interpolated trace on key GC performance statistics was investigated using retrospective data received from STAR GC in Christchurch Hospital ICU, New Zealand (2011-2015). RESULTS: All of the piecewise functions performed considerably better than the fitted interpolation functions. Linear piecewise interpolation performed the best having a mean RMSE 0.39 mmol/L, within 2 standard deviations of the BG sensor error. Minutely sampled BG resulted in significantly different key GC performance values when compared to raw sparse BG measurements. CONCLUSION: Linear piecewise interpolation provides the best estimate of intermediate BG dynamics and all analyses comparing GC protocol performance should use minutely linearly interpolated BG data.

Nutrition delivery of a model-based ICU glycaemic control system.

BACKGROUND: Hyperglycaemia is commonplace in the adult intensive care unit (ICU), associated with increased morbidity and mortality. Effective glycaemic control (GC) can reduce morbidity and mortality, but has proven difficult. STAR is a proven, effective model-based ICU GC protocol that uniquely maintains normo-glycaemia by changing both insulin and nutrition interventions to maximise nutrition in the context of GC in the 4.4-8.0 mmol/L range. Hence, the level of nutrition it provides is a time-varying estimate of the patient-specific ability to take up glucose. METHODS: First, the clinical provision of nutrition by STAR in Christchurch Hospital, New Zealand (N = 221 Patients) is evaluated versus other ICUs, based on the Cahill et al. survey of 158 ICUs. Second, the inter- and intra- patient variation of nutrition delivery with STAR is analysed. Nutrition rates are in terms of percentage of caloric goal achieved. RESULTS: Mean nutrition rates clinically achieved by STAR were significantly higher than the mean and best ICU surveyed, for the first 3 days of ICU stay. There was large inter-patient variation in nutrition rates achieved per day, which reduced overtime as patient-specific metabolic state stabilised. Median intra-patient variation was 12.9%; however, the interquartile range of the mean per-patient nutrition rates achieved was 74.3-98.2%, suggesting patients do not deviate much from their mean patient-specific nutrition rate. Thus, the ability to tolerate glucose intake varies significantly between, rather than within, patients. CONCLUSIONS: Overall, STAR's protocol-driven changes in nutrition rate provide higher nutrition rates to hyperglycaemic patients than those of 158 ICUs from 20 countries. There is significant inter-patient variability between patients to tolerate and uptake glucose, where intra-patient variability over stay is much lower. Thus, a best nutrition rate is likely patient specific for patients requiring GC. More importantly, these overall outcomes show high nutrition delivery and safe, effective GC are not exclusive and that restricting nutrition for GC does not limit overall nutritional intake compared to other ICUs.

Generalisability of a Virtual Trials Method for Glycaemic Control in Intensive Care.

BACKGROUND: Elevated blood glucose (BG) concentrations (Hyperglycaemia) are a common complication in critically ill patients. Insulin therapy is commonly used to treat hyperglycaemia, but metabolic variability often results in poor BG control and low BG (hypoglycaemia). OBJECTIVE: This paper presents a model-based virtual trial method for glycaemic control protocol design, and evaluates its generalisability across different populations. METHODS: Model-based insulin sensitivity (SI) was used to create virtual patients from clinical data from three different ICUs in New Zealand, Hungary, and Belgium. Glycaemic results from simulation of virtual patients under their original protocol (self-simulation) and protocols from other units (cross simulation) were compared. RESULTS: Differences were found between the three cohorts in median SI and inter-patient variability in SI. However, hour-to-hour intra-patient variability in SI was found to be consistent between cohorts. Self and cross-simulation results were found to have overall similarity and consistency, though results may differ in the first 24-48 h due to different cohort starting BG and underlying SI. CONCLUSIONS AND SIGNIFICANCE: Virtual patients and the virtual trial method were found to be generalisable across different ICUs. This virtual trial method is useful for in silico protocol design and testing, given an understanding of the underlying assumptions and limitations of this method.

Safety, efficacy and clinical generalization of the STAR protocol: a retrospective analysis.

BACKGROUND: The changes in metabolic pathways and metabolites due to critical illness result in a highly complex and dynamic metabolic state, making safe, effective management of hyperglycemia and hypoglycemia difficult. In addition, clinical practices can vary significantly, thus making GC protocols difficult to generalize across units.The aim of this study was to provide a retrospective analysis of the safety, performance and workload of the stochastic targeted (STAR) glycemic control (GC) protocol to demonstrate that patient-specific, safe, effective GC is possible with the STAR protocol and that it is also generalizable across/over different units and clinical practices. METHODS: Retrospective analysis of STAR GC in the Christchurch Hospital Intensive Care Unit (ICU), New Zealand (267 patients), and the Gyula Hospital, Hungary (47 patients), is analyzed (2011-2015). STAR Christchurch (BG target 4.4-8.0 mmol/L) is also compared to the Specialized Relative Insulin and Nutrition Tables (SPRINT) protocol (BG target 4.4-6.1 mmol/L) implemented in the Christchurch Hospital ICU, New Zealand (292 patients, 2005-2007). Cohort mortality, effectiveness and safety of glycemic control and nutrition delivered are compared using nonparametric statistics. RESULTS: Both STAR implementations and SPRINT resulted in over 86 % of time per episode in the blood glucose (BG) band of 4.4-8.0 mmol/L. Patients treated using STAR in Christchurch ICU spent 36.7 % less time on protocol and were fed significantly more than those treated with SPRINT (73 vs. 86 % of caloric target). The results from STAR in both Christchurch and Gyula were very similar, with the BG distributions being almost identical. STAR provided safe GC with very few patients experiencing severe hypoglycemia (BG < 2.2 mmol/L, <5 patients, 1.5 %). CONCLUSIONS: STAR outperformed its predecessor, SPRINT, by providing higher nutrition and equally safe, effective control for all the days of patient stay, while lowering the number of measurements and interventions required. The STAR protocol has the ability to deliver high performance and high safety across patient types, time, clinical practice culture (Christchurch and Gyula) and clinical resources.