Jack Ligtenberg

Accuracy and feasibility of point-of-care and continuous blood glucose analysis in critically ill ICU patients

IntroductionTo obtain strict glucose regulation, an accurate and feasible bedside glucometry method is essential. We evaluated three different types of point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The study was performed as a single-centre, prospective, observational study in a 12-bed medical ICU of a university hospital.MethodsPatients with an expected ICU stay of more than 48 hours were included. Because the reference laboratory delivers glucose values after approximately 30 to 60 minutes, which is too slow to use in a glucose regulation protocol and for calibration of the subcutaneous continuous glucose monitoring system (CGMS) (CGMS System Gold), we first validated the ICU-based blood gas/glucose analyser ABL715 (part 1 of the study). Subsequently, part 2 was performed: after inserting (and calibrating) the subcutaneous CGMS, heparinised arterial blood samples were drawn from an arterial line every 6 hours and analysed on both the Precision PCx point-of-care meter using test strips and on the blood gas/glucose analyser ABL715. CGMS glucose data were downloaded after 24 to 72 hours. The results of the paired measurements were analysed as a scatter plot by the method of Bland and Altman and were expressed as a correlation coefficient.ResultsPart 1: Four hundred and twenty-four blood samples were drawn from 45 critically ill ICU patients. The ICU-based blood gas/glucose analyser ABL715 provided a good estimate of conventional laboratory glucose assessment: the correlation coefficient was 0.95. In the Clarke error grid, 96.8% of the paired measurements were in the clinically acceptable zones A and B. Part 2: One hundred sixty-five paired samples were drawn from 19 ICU patients. The Precision PCx point-of-care meter showed a correlation coefficient of 0.89. Ninety-eight point seven percent of measurements were within zones A and B. The correlation coefficient for the subcutaneous CGMS System Gold was 0.89. One hundred percent of measurements were within zones A and B.ConclusionThe ICU-based blood glucose analyser ABL715 is a rapid and accurate alternative for laboratory glucose determination and can serve as a standard for ICU blood glucose measurements. The Precision PCx is a good alternative, but feasibility may be limited because of the blood sample handling. The subcutaneous CGMS System Gold is promising, but real-time glucose level reporting is necessary before it can be of clinical use in the ICU. When implementing a glucose-insulin algorithm in patient care or research, one should realise that the absolute glucose level may differ systematically among various measuring methods, influencing targeted glucose levels.

Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target?

Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and – despite many unanswered questions – therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial. We clearly need to understand better the mechanisms that underlie MODS. The endothelium certainly plays an active role in MODS. It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration. An important regulator of these systems is the angiopoietin/Tie2 signalling system. In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy.

Quality of interhospital transport of critically ill patients: a prospective audit

IntroductionThe aim of transferring a critically ill patient to the intensive care unit (ICU) of a tertiary referral centre is to improve prognosis. The transport itself must be as safe as possible and should not pose additional risks. We performed a prospective audit of the quality of interhospital transports to our university hospital-based medical ICU.MethodsTransfers were undertaken using standard ambulances. On departure and immediately after arrival, the following data were collected: blood pressure, heart rate, body temperature, oxygen saturation, arterial blood gas analysis, serum lactic acid, plasma haemoglobin concentration, blood glucose, mechanical ventilation settings, use of vasopressor/inotropic drugs, and presence of venous and arterial catheters. Ambulance personnel completed forms describing haemodynamic and ventilatory data during transport. Data were collected by our research nurse and analyzed.ResultsA total of 100 consecutive transfers of ICU patients over a 14-month period were evaluated. Sixty-five per cent of patients were mechanically ventilated; 38% were on vasoactive drugs. Thirty-seven per cent exhibited an increased number of vital variables beyond predefined thresholds after transport compared with before transport; 34% had an equal number; and 29% had a lower number of vital variables beyond thresholds after transport. The distance of transport did not correlate with the condition on arrival. Six patients died within 24 hours after arrival; vital variables in these patients were not significantly different from those in patients who survived the first 24 hours. ICU mortality was 27%. Adverse events occurred in 34% of transfers; in 50% of these transports, pretransport recommendations given by the intensivist of our ICU were ignored. Approximately 30% of events may be attributed to technical problems.ConclusionOn aggregate, the quality of transport in our catchment area carried out using standard ambulances appeared to be satisfactory. However, examination of the data in greater detail revealed a number of preventable events. Further improvement must be achieved by better communication between referring and receiving hospitals, and by strict adherence to checklists and to published protocols. Patients transported between ICUs are still critically ill and should be treated as such.

Quality of interhospital transport of the critically ill: impact of a Mobile Intensive Care Unit with a specialized retrieval team.

IntroductionIn order to minimize the additional risk of interhospital transport of critically ill patients, we started a mobile intensive care unit (MICU) with a specialized retrieval team, reaching out from our university hospital-based intensive care unit to our adherence region in March 2009. To evaluate the effects of this implementation, we performed a prospective audit comparing adverse events and patient stability during MICU transfers with our previous data on transfers performed by standard ambulance.MethodsAll transfers performed by MICU from March 2009 until December 2009 were included. Data on 14 vital variables were collected at the moment of departure, arrival and 24 hours after admission. Variables before and after transfer were compared using the paired-sample T-test. Major deterioration was expressed as a variable beyond a predefined critical threshold and was analyzed using the McNemar test and the Wilcoxon Signed Ranks test. Results were compared to the data of our previous prospective study on interhospital transfer performed by ambulance.ResultsA total of 74 interhospital transfers of ICU patients over a 10-month period were evaluated. An increase of total number of variables beyond critical threshold at arrival, indicating a worsening of condition, was found in 38 percent of patients. Thirty-two percent exhibited a decrease of one or more variables beyond critical threshold and 30% showed no difference. There was no correlation between patient status at arrival and the duration of transfer or severity of disease. ICU mortality was 28%. Systolic blood pressure, glucose and haemoglobin were significantly different at arrival compared to departure, although significant values for major deterioration were never reached. Compared to standard ambulance transfers of ICU patients, there were less adverse events: 12.5% vs. 34%, which in the current study were merely caused by technical (and not medical) problems. Although mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was significantly higher, patients transferred by MICU showed less deterioration in pulmonary parameters during transfer than patients transferred by standard ambulance.ConclusionsTransfer by MICU imposes less risk to critically ill patients compared to transfer performed by standard ambulance and has, therefore, resulted in an improved quality of interhospital transport of ICU patients in the north-eastern part of the Netherlands.

Hyperglycaemia in critically ill patients: marker or mediator of mortality?

Acute hyperglycaemia has been associated with complications, prolonged intensive care unit and hospital stay, and increased mortality. We made an inventory of the prevalence and prognostic value of hyperglycaemia, and of the effects of glucose control in different groups of critically ill patients. The prevalence of hyperglycaemia in critically ill patients, using stringent criteria, approaches 100%. An unambiguous negative correlation between hyperglycaemia and mortality has been described in various groups of critically ill patients. Although the available evidence remains inconsistent, there appears to be a favourable effect of glucose regulation. This effect on morbidity and mortality depends on patient characteristics. To be able to compare results of future studies involving glucose regulation, better definitions of hyperglycaemia (and consequently of normoglycaemia) and patient populations are needed.

The relative adrenal insufficiency syndrome revisited : which patients will benefit from low-dose steroids?

Purpose of reviewSeveral clinical studies have given rise to optimism about low-dose steroid treatment in patients with sepsis. It reduces time to shock reversal and may even have a positive effect on mortality. The pathophysiology of the relative adrenal insufficiency syndrome has not yet been determined, and the usefulness of basal and stimulated cortisol levels in diagnosing this syndrome is still uncertain. This review will examine recent evidence to elucidate these questions. Recent findingsStudies performed in more than 1000 patients in intensive care show convincingly that in general serum cortisol levels are increased. Basal or stimulated cortisol levels are at best useful to predict mortality in patients in intensive care, not to decide which patients to treat or when to discontinue treatment. Measuring free cortisol concentrations rather than total cortisol concentrations in critically ill patients may lead to new research strategies to identify the mode of action of low-dose steroid treatment. SummaryIt has been shown that low-dose corticosteroid administration to catecholamine-dependent patients in septic shock results in shock reversal. There seems to be a relative shortage of cortisol, because low-dose hydrocortisone administration resulting in cortisol levels as much as four times the already increased levels results in shock reversal. Strong evidence for a positive effect on mortality is still lacking, perhaps because of the relatively low number of patients investigated. A very important topic in interpreting studies is that total (free plus protein-bound) cortisol has been measured. Future studies should also measure free cortisol concentrations, which could add to our knowledge of the pathophysiology and treatment of the relative adrenal insufficiency syndrome. On the basis of current knowledge, there is no evidence to support a treatment strategy based on a random or stimulated cortisol level. At the moment, rapid hemodynamic improvement of catecholamine-dependent patients after the administration of low-dose corticosteroids still seems the best available clue to diagnosis.

Inhibition of p38 mitogen-activated protein kinase: Dose-dependent suppression of leukocyte and endothelial response after endotoxin challenge in humans

Objective We studied the activity of a single oral dose of RWJ-67657, a synthetic p38 mitogen-activated protein kinase inhibitor, in preventing dual leukocyte/endothelial activation after endotoxin infusion in healthy volunteers. Design Prospective placebo-controlled study. Setting Intensive care unit at a university medical center. Subjects Twenty-one healthy male volunteers. Interventions Endotoxin (4 ng/kg) as a 1-min infusion. According to randomization, the volunteers received placebo (n = 6) or 1400 mg (n = 4), 700 mg (n = 6), or 350 mg (n = 5) of RWJ-67657. Measurements and Main Results Neutrophil activation was investigated by analyzing the extent of membrane expression of adhesion markers by calibrated flow cytometry. Circulating intercellular adhesion molecule-1 and E-selectin were measured by enzyme-linked immunosorbent assays. The endotoxin-induced shedding of L-selectin was diminished in a dose-dependent manner (p < .0001). High-dose RWJ-67657 prevented up-regulation of the integrins CD11b (p < .01) and CD 66b (p < .01) on neutrophils. The endotoxin-induced increase in circulating intercellular adhesion molecule-1 and circulation E-selectin was almost completely prevented by high-dose RWJ-67657. Conclusion A single oral dose of RWJ-67657 prevented neutrophil and endothelial activation after endotoxin infusion.

Inter-hospital transport of critically ill patients; expect surprises

IntroductionInter-hospital transport of critically ill patients is increasing. When performed by specialized retrieval teams there are less adverse events compared to transport by ambulance. These transports are performed with technical equipment also used in an Intensive Care Unit (ICU). As a consequence technical problems may arise and have to be dealt with on the road. In this study, all technical problems encountered while transporting patients with our mobile intensive care unit service (MICU) were evaluated.MethodsFrom March 2009 until August 2011 all transports were reviewed for technical problems. The cause, solution and, where relevant, its influence on protocol were stated.ResultsIn this period of 30 months, 353 patients were transported. In total 55 technical problems were encountered. We provide examples of how they influenced transport and how they may be resolved.ConclusionThe use of technical equipment is part of intensive care medicine. Wherever this kind of equipment is used, technical problems will occur. During inter-hospital transports, without extra personnel or technical assistance, the transport team is dependent on its own ability to resolve these problems. Therefore, we emphasize the importance of having some technical understanding of the equipment used and the importance of training to anticipate, prevent and resolve technical problems. Being an outstanding intensivist on the ICU does not necessarily mean being qualified for transporting the critically ill as well. Although these are lessons derived from inter-hospital transport, they may also apply to intra-hospital transport.

Clinical review: Treatment of new-onset atrial fibrillation in medical intensive care patients: a clinical framework

Atrial fibrillation occurs frequently in medical intensive care unit patients. Most intensivists tend to treat this rhythm disorder because they believe it is detrimental. Whether atrial fibrillation contributes to morbidity and/or mortality and whether atrial fibrillation is an epiphenomenon of severe disease, however, are not clear. As a consequence, it is unknown whether treatment of the arrhythmia affects the outcome. Furthermore, if treatment is deemed necessary, it is not known what the best treatment is. We developed a treatment protocol by searching for the best evidence. Because studies in medical intensive care unit patients are scarce, the evidence comes mainly from extrapolation of data derived from other patient groups. We propose a treatment strategy with magnesium infusion followed by amiodarone in case of failure. Although this strategy seems to be effective in both rhythm control and rate control, the mortality remained high. A randomised controlled trial in medical intensive care unit patients with placebo treatment in the control arm is therefore still defendable.

Antidepressants self-poisoning and ICU admissions in a University Hospital in the Netherlands

Objectives: Many overdosed patients are admitted to an ICU. Antidepressants are frequently used. We examined clinical end-points of toxicity recorded during admission to our ICU of all antidepressants used in overdose. Design: Single centre; retrospective analysis, 5 consecutive years (1994 – 1998). Setting: Intensive and Respiratory Care Unit, Groningen University Hospital. Participants: 86 patients admitted to the ICU because of antidepressant self-poisoning — database of 258 consecutively admitted patients with (auto-) intoxication. Results: Significantly more patients were intoxicated with TCAs (65) compared with SSRIs (20; p < 0.05), despite the fact that the number of prescriptions of antidepressants in the community was greater for SSRIs than for TCAs. Patients intoxicated with TCAs needed significantly more often tracheal intubation (27/65 vs 7/20; p < 0.05), and these individuals had also significantly more often tachycardia (14 vs. 3) and QRS-complex widening (19 vs. 1), compared to those with non-TCA antidepressant intoxication (p < 0.05). Conclusions: TCA self-poisoning has remained the predominant cause of morbidity among patients with auto-intoxication admitted to our ICU in the previous years. The data from this ICU-population confirm previous evidence that SSRIs are safer in overdose than TCAs. This finding was not explained by more prescriptions in the community of TCAs compared with SSRIs. Physicians should be more reluctant in prescribing TCAs to depressed patients in whom the risk of self-poisoning is difficult to assess.