Towards a feasible algorithm for tight glycaemic control in critically ill patients: a systematic review of the literature

Introduction  

Tight glycaemic control is an important issue in the management of intensive care unit (ICU) patients. The glycaemic goals described by Van Den Berghe and colleagues in their landmark study of intensive insulin therapy appear difficult to achieve in a real life ICU setting. Most clinicians and nurses are concerned about a potentially increased frequency of severe hypoglycaemic episodes with more stringent glycaemic control. One of the steps we took before we implemented a glucose regulation protocol was to review published trials employing insulin/glucose algorithms in critically ill patients.     

Glycaemic control in Australia and New Zealand before and after the NICE-SUGAR trial: a translational study

Introduction

There is no information on the uptake of Intensive Insulin Therapy (IIT) before the Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial in Australia and New Zealand (ANZ) and on the bi-national response to the trial, yet such data would provide important information on the evolution of ANZ practice in this field. We aimed to study ANZ glycaemic control before and after the publication of the results of the NICE-SUGAR trial.

Methods

We analysed glucose control in critically ill patients across Australia and New Zealand during a two-year period before and after the publication of the NICE-SUGAR study. We used the mean first day glucose (Glu₁) (a validated surrogate of ICU glucose control) to define practice. The implementation of an IIT protocol was presumed if the median of Glu₁ measurements was <6.44 mmol/L for a given ICU. Hypoglycaemia was categorised as severe (glucose ≤2.2 mmol/L) or moderate (glucose ≤3.9 mmol/L).

Results

We studied 49 ICUs and 176,505 patients. No ICU practiced IIT before or after NICE-SUGAR. Overall, Glu₁ increased from 7.96 (2.95) mmol/L to 8.03 (2.92) mmol/L (P <0.0001) after NICE-SUGAR. Similar increases were noted in all patient subgroups studied (surgical, medical, insulin dependent diabetes mellitus, ICU stay >48/<48 hours). The rate of severe and moderate hypoglycaemia before and after NICE-SUGAR study were 0.59% vs. 0.55% (P =0.33) and 6.62% vs. 5.68% (P <0.0001), respectively. Both crude and adjusted mortalities declined over the study period.

Conclusions

IIT had not been adopted in ANZ before the NICE-SUGAR study and glycaemic control corresponded to that delivered in the control arm of NICE-SUGAR trial. There were only minor changes in practice after the trial toward looser glycaemic control. The rate of moderate hypoglycaemia and mortality decreased along with such changes.     

Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes

Introduction  

Glucagon-like peptide-1 (GLP-1) attenuates the glycaemic response to small intestinal nutrient infusion in stress-induced hyperglycaemia and reduces fasting glucose concentrations in critically ill patients with type-2 diabetes. The objective of this study was to evaluate the effects of acute administration of GLP-1 on the glycaemic response to small intestinal nutrient infusion in critically ill patients with pre-existing type-2 diabetes.     

Intensive insulin therapy: enhanced Model Predictive Control algorithm versus standard care

Objective  To investigate the effectiveness of an enhanced software Model Predictive Control (eMPC) algorithm for intravenous insulin infusion, targeted at tight glucose control in critically ill patients, over 72 h, in two intensive care units with different management protocols. Design  Comparison with standard care in a two center open randomized clinical trial. Setting  Two adult intensive care units in University Hospitals. Patients and participants  Thirty-four critically ill patients with hyperglycaemia (glucose >120 mg/dL) or already receiving insulin infusion. Interventions  Patients were randomized, within each ICU, to intravenous insulin infusion advised by eMPC algorithm or the ICU’s standard insulin infusion administration regimen. Measurements and results  Arterial glucose concentration was measured at study entry and when advised by eMPC or measured as part of standard care. Time-weighted average glucose concentrations in patients receiving eMPC advised insulin infusions were similar [104 mg/dL (5.8 mmol/L)] in both ICUs. eMPC advised glucose measurement interval was significantly different between ICUs (1.1 vs. 1.8 h, P < 0.01). The standard care insulin algorithms resulted in significantly different time-weighted average glucose concentrations between ICUs [128 vs. 99 mg/dL (7.1 vs. 5.5 mmol/L), P < 0.01]. Conclusions  In this feasibility study the eMPC algorithm provided similar, effective and safe tight glucose control over 72 h in critically ill patients in two different ICUs. Further development is required to reduce glucose sampling interval while maintaining a low risk of hypoglycaemia. An erratum to this article can be found at     

Uncertainties in the measurement of blood glucose in paediatric intensive care: implications for clinical trials of tight glycaemic control

Purpose  

In preparation for a tight glycaemic control (TGC) clinical trial we assessed the agreement between methods used to measure blood glucose in critically ill children.     

Antipyretic therapy in febrile critically ill adults: A systematic review and meta-analysis

Purpose

To determine whether fever control with antipyretic therapy effects the mortality of febrile critically ill adults.

Methods

Systematic review using MEDLINE, EMBASE, Cochrane Central Register for Controlled Trials, CINAHL, Google Scholar, and 2 clinical trial registries from inception to April 2012. Randomized clinical trials comparing treatment of fever with no treatment or comparing different thresholds for fever control in adults without acute neurological injury admitted to intensive care units (ICUs) were selected for review. The effect of fever control on all-cause ICU-mortality was determined using a random effects meta-analysis.

Results

Five randomized clinical trials in 399 patients were included. The temperature threshold for treatment in the intervention group was commonly 38.3°C to 38.5°C, whereas it was typically 40.0°C for controls. Four studies used physical measures and 3 used pharmacologic measures for temperature control. There was no significant heterogeneity among the included studies (I² = 12.5%, P = .3). Fever control did not significantly effect ICU mortality with a pooled risk ratio of 0.98 (95% confidence interval 0.58-1.63, P = .9).

Conclusions

This meta-analysis found no evidence that fever treatment influences mortality in critically ill adults without acute neurological injury. However, studies were underpowered to detect clinically important differences.     

Impact of nosocomial infections on clinical outcome and resource consumption in critically ill patients

Objective  

Nosocomial infections still present a major problem in intensive care units (ICUs), accounting for prolonged ICU and hospital stays and worsened outcomes. There exist differences in the literature regarding the impact of nosocomial infections on attributable mortality and resource consumption. The aim of this study was to observe these effects in a large cohort of critically ill patients.     

Occurrence and adverse effect on outcome of hyperlactatemia in the critically ill

Introduction  

Hyperlactatemia is frequent in critically ill patients and is often used as a marker of adverse outcome. However, studies to date have focused on selected intensive care unit (ICU) populations. We sought to determine the occurrence and relation of hyperlactatemia with ICU mortality in all patients admitted to four ICUs in a large regional critical care system.     

Continuous glucose monitors prove highly accurate in critically ill children

Introduction  

Hyperglycemia is associated with increased morbidity and mortality in critically ill patients and strict glycemic control has become standard care for adults. Recent studies have questioned the optimal targets for such management and reported increased rates of iatrogenic hypoglycemia in both critically ill children and adults. The ability to provide accurate, real-time continuous glucose monitoring would improve the efficacy and safety of this practice in critically ill patients. The aim of our study is to determine if a continuous, interstitial glucose monitor will correlate with blood glucose values in critically ill children.     

A research algorithm to improve detection of delirium in the intensive care unit

Introduction  

Delirium is a serious and prevalent problem in intensive care units (ICUs). The purpose of this study was to develop a research algorithm to enhance detection of delirium in critically ill ICU patients using chart review to complement a validated clinical delirium instrument.     

Characteristics and outcomes of cancer patients in European ICUs

Introduction  

Increasing numbers of cancer patients are being admitted to the intensive care unit (ICU), either for cancer-related complications or treatment-associated side effects, yet there are relatively few data concerning the epidemiology and prognosis of cancer patients admitted to general ICUs. The aim of this study was to assess the characteristics of critically ill cancer patients, and to evaluate their prognosis.     

Epidemiology of critically ill patients in intensive care units: a population-based observational study

Introduction

Epidemiologic assessment of critically ill people in Intensive Care Units (ICUs) is needed to ensure the health care system can meet current and future needs. However, few such studies have been published.

Methods

Population-based analysis of all adult ICU care in the Canadian province of Manitoba, 1999 to 2007, using administrative data. We calculated age-adjusted rates and trends of ICU care, overall and subdivided by age, sex and income.

Results

In 2007, Manitoba had a population of 1.2 million, 118 ICU beds in 21 ICUs, for 9.8 beds per 100,000 population. Approximately 0.72% of men and 0.47% of women were admitted to ICUs yearly. The age-adjusted, male:female rate ratio was 1.75 (95% CI 1.64 to 1.88). Mean age was 64.5 ± 16.4 years. Rates rose rapidly after age 40, peaked at age 75 to 80, and declined for the oldest age groups. Rates were higher among residents of lower income areas, for example declining from 7.9 to 4.4 per 100,000 population from the poorest to the wealthiest income quintiles (p <0.0001). Rates of ICU admission slowly declined over time, while cumulative yearly ICU bed-days slowly rose; changes were age-dependent, with faster declines in admission rates with older age. There was a high rate of recidivism; 16% of ICU patients had received ICU care previously.

Conclusions

These temporal trends in ICU admission rates and cumulative bed-days used have significant implications for health system planning. The differences by age, sex and socioeconomic status, and the high rate of recidivism require further research to clarify their causes, and to devise strategies for reducing critical illness in high-risk groups.     

Diagnosis and management of temperature abnormality in ICUs: a EUROBACT investigators' survey

Introduction

Although fever and hypothermia are common abnormal physical signs observed in patients admitted to intensive care units (ICU), little data exist on their optimal management. The objective of this study was to describe contemporary practices and determinants of management of temperature abnormalities among patients admitted to ICUs.

Methods

Site leaders of the multi-national EUROBACT study were surveyed regarding diagnosis and management of temperature abnormalities among patients admitted to their ICUs.

Results

Of the 162 ICUs originally included in EUROBACT, responses were received from 139 (86%) centers in 23 countries in Europe (117), South America (8), Asia (5), North America (4), Australia (3) and Africa (2). A total of 117 (84%) respondents reported use of a specific temperature threshold in their ICU to define fever. A total of 14 different discrete levels were reported with a median of 38.2°C (inter-quartile range, IQR, 38.0°C to 38.5°C). The use of thermometers was protocolized in 91 (65%) ICUs and a wide range of methods were reportedly used, with axillary, tympanic and urinary bladder sites as the most common as primary modalities. Only 31 (22%) of respondents indicated that there was a formal written protocol for temperature control among febrile patients in their ICUs. In most or all cases practice was to control temperature, to use acetaminophen, and to perform a full septic workup in febrile patients and that this was usually directed by physician order. While reported practice was to treat nearly all patients with neurological impairment and most patients with acute coronary syndromes and infections, severe sepsis and septic shock, this was not the case for most patients with liver failure and fever.

Conclusions

A wide range of definitions and management practices were reported regarding temperature abnormalities in the critically ill. Documenting temperature abnormality management practices, including variability in clinical care, is important to inform planning of future studies designed to optimize infection and temperature management strategies in the critically ill.     

Time series analysis of use patterns for common invasive technologies in critically ill patients

Purpose

Critically ill patients are frequently managed with invasive technologies as part of their medical care. Little is known about use patterns. We examined use trends for invasive technologies used in critically ill patients.

Materials and Methods

Using time series analysis and data on 26?989 patients from 3 medical-surgical intensive care units (ICUs) (n = 18?224) and 1 surgical ICU (n = 8765) between January 1, 1999, and January 1, 2007, we measured changes in the proportion of patients receiving the 4 most frequently used invasive technologies used in critically ill patients.

Results

The 4 most common invasive technologies used in critically ill patients during the study period were arterial lines (71%), endotracheal intubations (61%), central venous catheters (51%), and pulmonary artery catheters (18%). The proportion of ICU patients who received pulmonary artery catheters decreased from 25% in 1999 to 8% in 2006 (P < .001). Use of central venous catheters increased from 39% to 46% (P < .001). After adjusting for baseline characteristics, patients admitted in 2006 were 4 times less likely to receive a pulmonary artery catheter (odds ratio, 0.28; 95% confidence interval, 0.24-0.33), but 42% (odds ratio, 1.42; 95% confidence interval, 1.27-1.58) more likely to receive a central venous catheter than patients admitted in 1999. No significant changes were observed for intubations and arterial lines.

Conclusions

The use of invasive technologies in critically ill patients is changing and may have important implications for resource use, clinician education, and patient care. Initiatives should be considered for ensuring clinician competency during technology transitions.     

The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia in medical-surgical intensive care units

Introduction

Although sodium disturbances are common in hospitalised patients, few studies have specifically investigated the epidemiology of sodium disturbances in the intensive care unit (ICU). The objectives of this study were to describe the incidence of ICU-acquired hyponatraemia and hypernatraemia and assess their effects on outcome in the ICU.

Methods

We identified 8142 consecutive adults (18 years of age or older) admitted to three medical-surgical ICUs between 1 January 2000 and 31 December 2006 who were documented to have normal serum sodium levels (133 to 145 mmol/L) during the first day of ICU admission. ICU acquired hyponatraemia and hypernatraemia were respectively defined as a change in serum sodium concentration to below 133 mmol/L or above 145 mmol/L following day one in the ICU.

Results

A first episode of ICU-acquired hyponatraemia developed in 917 (11%) patients and hypernatraemia in 2157 (26%) patients with an incidence density of 3.1 and 7.4 per 100 days of ICU admission, respectively, during 29,142 ICU admission days. The incidence of both ICU-acquired hyponatraemia (age, admission diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, length of ICU stay, level of consciousness, serum glucose level, body temperature, serum potassium level) and ICU-acquired hypernatraemia (baseline creatinine, APACHE II score, mechanical ventilation, length of ICU stay, body temperature, serum potassium level, level of care) varied according to patients' characteristics. Compared with patients with normal serum sodium levels, hospital mortality was increased in patients with ICU-acquired hyponatraemia (16% versus 28%, p < 0.001) and ICU-acquired hypernatraemia (16% versus 34%, p < 0.001).

Conclusions

ICU-acquired hyponatraemia and hypernatraemia are common in critically ill patients and are associated with increased risk of hospital mortality.     

Critical care outreach during the COVID-19 pandemic: An observational study

Background

Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, the Critical Care Outreach Team (CCOT) remained operational to provide critical care support to acutely ill and deteriorating patients on the wards.

Aim

We aimed to evaluate the demand and efficacy of the critical care outreach service during the COVID-19 pandemic.

Method

We prospectively evaluated all patients referred to critical care outreach enrolled during a twelve-month period. We reported the cumulative number of activities and interventions and baseline characteristics, acuity level and patients' clinical outcome. The rate of ICU admissions, activity plan, patients' acuity and mortality are compared to historical data pre-pandemic.

Results

Amongst 4849 patients referred, 3913 had a clinical review and of those 895 were COVID-19 positive. Non-invasive ventilation was mostly delivered to COVID-19 patients (COVID-19 +VE: 853/895, 95% vs. COVID-19 −VE: 119/3018, 4%) alongside awake prone positioning (COVID-19 +VE: 232/895, 26% vs. COVID-19 −VE: 0/3018, 0%). Compared to pre-pandemic, the cumulative number of patients assessed increased (observed: 3913 vs. historical: 3615; p = 0.204), patients meeting Level 2 acuity were higher (observed: 51% vs. historical: 21%; p = 0.003), but ICU admission rate did not increase significantly (observed: 12% vs. historical: 9%; p = 0.065), and greater mortality rate (observed: 14% vs. historical: 8%; p = 0.046) was observed.

Conclusion

Critical care outreach bridges the gap between the intensive care unit and general wards and supports the concept of ‘critical care without walls’ acting as a valuable resource in optimizing and triaging acutely unwell patients and potentially averting critical care admissions.

Relevance to Clinical Practice

The COVID-19 pandemic has generated an unprecedented surge of deteriorating and critically ill patients with has caused severe and sustained pressures on intensive care units (ICUs) and general wards. Acutely ill patients can deteriorate quickly, and early recognition is vital to commence critical intervention on the wards or transfer timely to ICU. The Critical Care Outreach Team can help staff and optimize acutely ill and deteriorating patients by providing timely critical care interventions at the patient bedside.     

Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults

Objective Aggressive glycemic control improves mortality and morbidity in critically ill adults, however implementation of such a strategy can be logistically difficult. This study evaluates the efficiency and safety of a nurse-managed insulin protocol in critically ill adults.Design Combined retrospective-prospective before-after cohort study.Setting Twenty-one bed, medical/surgical ICU in a tertiary care hospital.Patients Two cohorts of 50 consecutive ICU patients requiring insulin infusions.Intervention Patients in the control cohort received insulin infusions titrated according to target blood glucose ranges and sliding scales at the physicians discretion. Patients in the interventional cohort received an insulin infusion adjusted using a standardized protocol targeting a blood glucose of 4.5–6.1 mmol/l (81–110 mg/dl).Measurements and main results Efficiency was measured by comparing the time to reach, and the time spent within, the target range between cohorts. Safety was assessed by comparing the incidence of severe hypoglycemia, the frequency of rescue dextrose administration and the cumulative time that the infusion was held for hypoglycemia between cohorts. Patients in the interventional cohort reached their target more rapidly (11.3±7.9 vs 16.4±12.6 h; p=0.028) and maintained their blood glucose within the target range longer (11.5±3.7 vs 7.1±5.0 h/day; p<0.001) than controls. The standardized protocol yielded a four-fold reduction in the incidence of severe hypoglycemia (4 vs 16%; p=0.046) and reduced the median frequency of dextrose rescue therapy (0 [0–0.91] vs 0.17 [0–1.2] episodes/patient per day; p=0.01) as compared to controls.Conclusion Standardization of intensive insulin therapy improves the efficiency and safety of glycemic control in critically ill adults.     

Early or late parenteral nutrition: ASPEN vs. ESPEN

Citation

Casaer MP, Mesotten D, Hermans G et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365: 506-517.

Background

Controversy exists about the timing of the initiation of parenteral nutrition (PN) in critically ill adults in whom caloric targets cannot be met by enteral nutrition (EN) alone.

Methods

Objective

To compare early-initiation of PN (European guidelines) with late-initiation (American and Canadian guidelines) in adults who are receiving insufficient enteral nutrition in the intensive care unit (ICU).

Design

Prospective, randomized, controlled, parallel-group, multicenter clinical trial.

Setting

Seven multidisciplinary ICUs in Belgium.

Subjects

All adults admitted to participating ICUs with a nutritional risk score of 3 or more who did not meet any exclusion criteria.

Intervention

After enrollment, 2312 patients were randomized to receive PN 48 hours after ICU admission (early-initiation) and 2328 patients were randomized to receive PN on day 8 (late-initiation group). Both groups received early EN using a standardized protocol. PN was continued until EN met 80% of calorific goals, or when oral nutrition was resumed. It was restarted if enteral or oral feeding fell below 50% of calculated calorific needs.

Outcomes

Primary end point was the duration of dependency on intensive care, defined as the number of intensive care days and time to discharge from the ICU.

Results

The median stay in the ICU was one day shorter for the late-initiation group (3 v. 4; p = 0.02). The late-initiation group had a relative increase, of 6.3%, in the likelihood of being discharged earlier, and alive, from the ICU (hazard ratio 1.06; 95% confidence interval [CI] 1.00-1,13; p = 0.04). Rates of death in the ICU and survival at 90 days were similar between the two groups. The late-initiation group, as compared to the early-initiation group, had fewer ICU infections (22.8% v. 26.2%; p = 0.008), less days of renal replacement therapy (7 days (interquartile range [IQR] 3-16) v. 10 days (IQR 5-23); p = 0.008) and fewer patients requiring more than 2 days of mechanical ventilation (36.3% v. 40.2%; p = 0.006).

Conclusions

Late-initiation of PN was associated with faster recovery and fewer complications, when compared with early-initiation.

Trial Registration

{"type":"clinical-trial","attrs":{"text":"NCT00512122","term_id":"NCT00512122"}}NCT00512122     

Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients

Introduction  

Blood glucose levels and insulin resistance in critically ill patients on admission to intensive care units (ICUs) have been identified as factors influencing mortality. The pathogenesis of insulin resistance (IR) in critically ill patients is complex and not fully understood. Resistin is a hormone mainly derived from macrophages in humans and from adipose tissue in rodents, which regulates glucose metabolism and insulin sensitivity. In non-critically ill patients, resistin was found to be related to impaired glucose tolerance, insulin resistance, metabolic syndrome, obesity and type 2 diabetes. Therefore, resistin might represent a link between inflammation, acute phase response and insulin resistance in critically ill patients. We aimed to examine the correlation of serum resistin concentrations to parameters of inflammation, organ function, metabolism, disease severity and survival in critically ill patients.