Oliver Flower

Use of an Intravascular Fluorescent Continuous Glucose Sensor in ICU Patients

Background: Hyperglycemia and hypoglycemia are associated with adverse clinical outcomes in intensive care patients. In product development studies at 4 ICUs, the safety and performance of an intravascular continuous glucose monitoring (IV-CGM) system was evaluated in 70 postsurgical patients. Methods: The GluCath System (GluMetrics, Inc) used a quenched chemical fluorescence mechanism to optically measure blood glucose when deployed via a radial artery catheter or directly into a peripheral vein. Periodic ultrasound assessed blood flow and thrombus formation. Patient glucose levels were managed according to the standard of care and existing protocols at each site. Reference blood samples were acquired hourly and compared against prospectively calibrated sensor results. Results: In all, 63 arterial sensors and 9 venous sensors were deployed in 70 patients. Arterial sensors did not interfere with invasive blood pressure monitoring, sampling or other aspects of patient care. A majority of venous sensors (66%) exhibited thrombus on ultrasound. In all, 89.4% (1383/1547) of arterial and 72.2% (182/252) of venous measurements met ISO15197:2003 criteria (within 20%), and 72.7% (1124/1547) of arterial and 56.3% (142/252) of venous measurements met CLSI POCT 12-A3 criteria (within 12.5%). The aggregate mean absolute relative difference (MARD) between the sensors and the reference was 9.6% for arterial and 14.2% for venous sensors. Conclusions: The GluCath System exhibited acceptable accuracy when deployed in a radial artery for up to 48 hours in ICU patients after elective cardiac surgery. Accuracy of venous deployment was substantially lower with significant rates of intravascular thrombus observed using ultrasound.

Glucose control in critically ill patients

Opinions regarding the control of blood glucose in critically ill patients have fluctuated dramatically over the past decade, and while our knowledge is far greater than in 2001, many questions remain unanswered. Hyperglycaemia is highly prevalent during critical illness, with 90% of patients treated in intensive care units (ICU) experiencing blood glucose concentrations greater than 6.1 mmol/L. The hypermetabolic ‘stress’ state is associated with both increased hepatic glucose production and peripheral insulin resistance, which is compounded by the hyperglycaemic effects of treatments, such as corticosteroids, sympathomimetic agents and glucose containing infusions. During the 1990s, the prevailing opinion was that hyperglycaemia was a normal and potentially beneficial physiological response to critical illness that promoted cellular glucose uptake. Standard care was to tolerate hyperglycaemia as an adaptive response and to start insulin only when blood glucose concentration exceeded the renal threshold (12 mmol/L or 215 mg/dL), with the goal of preventing glycosuria and hypovolaemia. Opinions began to alter after the DIGAMI (Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction) trial was published in 1995. In that trial, more intensive glucose control (IGC) to maintain a blood glucose concentration below 11.9 mmol/L resulted in improved long-term outcome in patients with diabetes who had suffered acute myocardial infarction. A far greater shift in opinion occurred following the publication of Van den Berghe’s landmark paper in 2001. Van den Berghe compared IGC (target blood glucose concentration between 4.4 and 6.1 mmol/L (80–110 mg/dL)) with conventional control (blood glucose treated when it exceeded 12.0 mmol/L (216 mg/dL)) with subsequent target of 10.0–11.1 mmol/L (180–200 mg/dL) in patients treated in a surgical ICU in Leuven, Belgium. The trial recruited 1548 patients and reported that intensive glucose control resulted in a 34% reduction in the risk of in-hospital death. The external validity of the trial was questioned because of the high mortality rate in both arms, being a single centre study, lack of blinding, excessive administration of intravenous glucose (200–300 g/ day) and early termination after multiple looks at the data. Despite these concerns, IGC became a recommended if not mandated treatment. Studies designed to confirm Van den Berghe’s findings reported less encouraging results. In 2006, Van den Bergh reported a near identical trial in the medical ICU at the same hospital in Leuven. In the second trial, in-hospital mortality was not significantly reduced although there was evidence of reduced morbidity in the form of reduced time to weaning from mechanical ventilation, reduced acute kidney injury and reduced time to discharge from both the ICU and the hospital. The first multicentre trial examined the role of IGC in patients with severe sepsis treated in 18 academic tertiary centres in Germany. The trial was stopped early for safety reasons because patients randomised to IGC suffered a significantly increased incidence of severe hypoglycaemia, without any evidence of a beneficial effect on either 28or 90-day mortality. Despite this, guidelines continued to recommend IGC. The Glucontrol study was another multicentre trial in Europe that compared the effect of IGC and conventional glucose control (target blood glucose, 7.8–10.0 mmol/L (140–180 mg/dL)) on the mortality of patients admitted to 21 medical-surgical ICU. Although designed to recruit 3500 patients, the trial was stopped early because of a high number of protocol violations after the recruitment of 1078 patients. The trial also reported no significant difference in ICU mortality (17.2% for IGC vs 15.3% for conventional treatment, P = 0.41) and again an increased rate of hypoglycaemia in the IGC group (8.7% vs 2.7%, P < 0.0001). Despite several trials and meta-analyses concluding there was no significant benefit from IGC, it took the publication of The Normoglycemia in Intensive Care Evaluation – Survival Using Glucose Algorithm Regulation (NICE-SUGAR) Study to change practice recommendations. The NICE-SUGAR study examined the effect of IGC on 90-day all-cause mortality in 6104 critically ill patients drawn from 42 hospitals in Australia, New Zealand, Canada and the United States. The primary outcome measure was available for 6022 patients, and those assigned to IGC had an increased risk of death (27.5% vs 24.9%, P = 0.02). This increased risk of death occurred despite a lower rate of hypoglycaemia in the IGC group than that reported in previous studies of combined surgical and medical patients. Meta-analyses have subsequently included the NICE-SUGAR data and concluded more strongly that IGC is not beneficial in critically ill patients and that it does increase the risk of severe hypoglycaemia.

Subarachnoid Hemorrhage Patients Admitted to Intensive Care in Australia and New Zealand: A Multicenter Cohort Analysis of In-Hospital Mortality Over 15 Years

Objective: The primary aim of this study was to describe in-hospital mortality in subarachnoid hemorrhage patients requiring ICU admission. Secondary aims were to identify clinical characteristics associated with inferior outcomes, to compare subarachnoid hemorrhage mortality with other neurological diagnoses, and to explore the variability in subarachnoid hemorrhage standardized mortality ratios. Design: Multicenter, binational, retrospective cohort study. Setting: Data were extracted from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. Patients: All available records for the period January 2000 to June 2015. Interventions: Nil. Measurements and Main Results: A total of 11,327 subarachnoid hemorrhage patients were identified in the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. The overall case fatality rate was 29.2%, which declined from 35.4% in 2000 to 27.2% in 2015 (p = 0.01). Older age, nonoperative admission, mechanical ventilation, higher Acute Physiology and Chronic Health Evaluation III scores, lower Glasgow Coma Scale, and admission prior to 2004 were all associated with lower hospital survival in multivariable analysis (p < 0.05). In comparison with other neurological diagnoses, subarachnoid hemorrhage patients had significantly greater risk-adjusted in-hospital mortality (odds ratio, 1.89 [95% CI, 1.79–2.00]). Utilizing data from the 5 most recent complete years (2010–2014), three sites had higher and four (including the two largest centers) had lower standardized mortality ratios than might be expected due to chance. Conclusions: Subarachnoid hemorrhage patients admitted to ICU in Australia and New Zealand have a high mortality rate. Year of admission beyond 2003 did not impact risk-adjusted in-hospital mortality. Significant variability was noted between institutions. This implies an urgent need to systematically evaluate many aspects of the critical care provided to this patient group.

Review article: Why is there still a debate regarding the safety and efficacy of intravenous thrombolysis in the management of presumed acute ischaemic stroke? A systematic review and meta-analysis

The objective of the present study is to independently and systematically assess the harms and benefits of intravenous thrombolysis for patients with presumed acute schaemic stroke.

Emergency Neurological Life Support: Acute Non-traumatic Weakness.

Acute non-traumatic weakness may be life threatening if it involves the respiratory muscles or is associated with autonomic dysfunction. Most patients presenting with acute muscle weakness have a worsening neurological disorder that requires a rapid, systematic evaluation, and detailed neurological exam to localize the disorder. Urgent laboratory tests and neuroimaging are needed in many patients to make the diagnosis. Because acute weakness is a common presenting sign of neurological emergencies, it was chosen as an Emergency Neurological Life Support protocol. Causes of acute non-traumatic weakness are discussed by both presenting clinical signs and anatomical location. For each diagnosis, key features of the history, examination, investigations, and treatment are outlined in the included tables.

Human Albumin Use in Adults in U.s. Academic Medical Centers.

Objective: To determine rates and predictors of albumin administration, and estimated costs in hospitalized adults in the United States. Design: Cohort study of adult patients from the University HealthSystem Consortium database from 2009 to 2013. Setting: One hundred twenty academic medical centers and 299 affiliated hospitals. Patients: A total of 12,366,264 hospitalization records. Interventions: Analysis of rates and predictors of albumin administration, and estimated costs. Measurements and Main Results: Overall the proportion of admissions during which albumin was administered increased from 6.2% in 2009 to 7.5% in 2013; absolute difference 1.3% (95% CI, 1.30–1.40%; p < 0.0001). The increase was greater in surgical patients from 11.7% in 2009 to 15.1% in 2013; absolute difference 3.4% (95% CI, 3.26–3.46%; p < 0.0001). Albumin use varied geographically being lowest with no increase in hospitals in the North Eastern United States (4.9% in 2009 and 5.3% in 2013) and was more common in bigger (> 750 beds; 5.2% in 2009 and 7.3% in 2013) compared to smaller hospitals (< 250 beds; 4.4% in 2009 to 6.2% in 2013). Factors independently associated with albumin use were appropriate indication for albumin use (odds ratio, 65.220; 95% CI, 62.459–68.103); surgical admission (odds ratio, 7.942; 95% CI, 7.889–7.995); and high severity of illness (odds ratio, 8.933; 95% CI, 8.825–9.042). Total estimated albumin cost significantly increased from

Improving care standards for patients with spinal trauma combining a modified e-Delphi process and stakeholder interviews: a study protocol.

325 million in 2009 to

Respiratory care of patients with cervical spinal cord injury: a review

468 million in 2013; (absolute increase of

Continuous intra-arterial blood glucose monitoring using quenched fluorescence sensing: a product development study.

233 million), p value less than 0.0001. Conclusions: The proportion of hospitalized adults in the United States receiving albumin has increased, with marked, and currently unexplained, geographic variability and variability by hospital size.

Continuous intra-arterial blood glucose monitoring using quenched fluorescence sensing in intensive care patients after cardiac surgery: phase II of a product development study.

Introduction Around 300 people sustain a new traumatic spinal cord injury (TSCI) in Australia each year; a relatively low incidence injury with extremely high long-term associated costs. Care standards are inconsistent nationally, lacking in consensus across important components of care such as prehospital spinal immobilisation, timing of surgery and timeliness of transfer to specialist services. This study aims to develop ‘expertly defined’ and agreed standards of care across the majority of disciplines involved for these patients. Methods and analysis A modified e-Delphi process will be used to gain consensus for best practice across specific clinical early care areas for the patient with TSCI; invited participants will include clinicians across Australia with relevant and significant expertise. A rapid literature review will identify available evidence, including any current guidelines from 2005 to 2015. Level and strength of evidence identified, including areas of contention, will be used to formulate the first round survey questions and statements. Participants will undertake 2–3 online survey rounds, responding anonymously to questionnaires regarding care practices and indicating their agreement or otherwise with practice standard statements. Relevant key stakeholders, including patients, will also be interviewed face to face. Ethics and dissemination Ethics approval for this study was obtained by the NSW Population & Health Services Research Ethics Committee on 14 January 2016 (HREC/12/CIPHS/74). Seeking comprehensive understanding of how the variation in early care pathways and treatment can be addressed to achieve optimal patient outcomes and economic costs; the overall aim is the agreement to a consistent approach to the triage, treatment, transport and definitive care of acute TSCI victims. The agreed practice standards of care will inform the development of a Clinical Pathway with practice change strategies for implementation. These standards will offer a benchmark for state-wide and potentially national policy.