Faculty Bibliography

INTRODUCTION: Esophagectomy with gastric tube reconstruction is characterized by high postoperative morbidity rates. Recently it was shown that decreased sublingual microvascular blood flow (MBF) preoperatively was associated with increased rate of complications after abdominal surgery. Similar observations in severely septic patients could be treated with dobutamine, independent of cardiac output. Based on these considerations we hypothesized that sublingual MBF derangements are more likely to be found in patients undergoing high risk surgery such as esophagectomy, and if present, might be prevented with administration of low dose dobutamine. METHODS: In this single-centre, prospective, double-blinded study, we randomized 20 patients admitted to the Intensive Care Unit following esophagectomy with gastric tube reconstruction into two groups. The intervention group (D) received a small dose of dobutamine (2.5 mug/kg/min) directly postoperative until two days postoperatively, whereas the placebo group (P) received a similar volume of saline. A subset of patients undergoing pancreaticoduodenectomy surgery was included as control group (C) for comparison with the study group. Sublingual MBF was determined one day prior to surgery until two days postoperatively. RESULTS: At the first postoperative day, patients in the esophagectomy/placebo group (P), showed a significant lower microvascular flow index, perfused vessel density and proportion of perfused vessels compared to baseline (p < 0.001) and the pancreaticoduodenectomy group (C) (p < 0.001). Administration of dobutamine significantly prevented the overall decrease in microvascular blood flow the first postoperative day. CONCLUSION: Postoperative sublingual MBF is markedly impaired in esophagectomy patients compared to patients who underwent a pancreaticoduodenectomy and could be prevented by early administration of a small dose dobutamine.

INTRODUCTION: We studied whether the choice of timing of discussing organ donation for the first time with the relatives of a patient with catastrophic brain injury in The Netherlands has changed over time and explored its possible consequences. Second, we investigated how thorough the process of brain death determination was over time by studying the number of medical specialists involved. And we studied the possible influence of the Donor Register on the consent rate. METHODS: We performed a retrospective chart review of all effectuated brain dead organ donors between 1987 and 2009 in one Dutch university hospital with a large neurosurgical serving area. RESULTS: A total of 271 medical charts were collected, of which 228 brain dead patients were included. In the first period, organ donation was discussed for the first time after brain death determination (87%). In 13% of the cases, the issue of organ donation was raised before the first EEG. After 1998, we observed a shift in this practice. Discussing organ donation for the first time after brain death determination occurred in only 18% of the cases. In 58% of the cases, the issue of organ donation was discussed before the first EEG but after confirming the absence of all brain stem reflexes, and in 24% of the cases, the issue of organ donation was discussed after the prognosis was deemed catastrophic but before a neurologist or neurosurgeon assessed and determined the absence of all brain stem reflexes as required by the Dutch brain death determination protocol. CONCLUSIONS: The phases in the process of brain death determination and the time at which organ donation is first discussed with relatives have changed over time. Possible causes of this change are the introduction of the Donor Register, the reintroduction of donation after circulatory death and other logistical factors. It is unclear whether the observed shift contributed to the high refusal rate in The Netherlands and the increase in family refusal in our hospital in the second studied period. Taking published literature on this subject into account, it is possible that this may have a counterproductive effect.

BACKGROUND: The choice of wording in cases of suspected brain death is important. If brain death has not been proven by electrocerebral silence and by absence of spontaneous breathing in an apnoea test in a patient in intensive care, then words like 'brain dead', 'has died' and 'clinical brain death' should be avoided in conversations with the relatives of the patient. This is illustrated by three cases. CASES: The first patient was a 46-year-old woman, with thrombosis of the basilar artery; the second was a 26-year-old man who was resuscitated after a bilateral pneumothorax, but developed severe postanoxic encephalopathy; and the third patient was a 64-year-old man with a large intracerebral haemorrhage. The relatives were informed that the patient was 'brain dead' or 'deceased' based on loss of consciousness (Glasgow Coma score of 3) and absence of brain stem reflexes, but prior to the completion of the brain death protocol by electroencephalography and apnoea testing. In the first and third cases, brain death could not be proven, and the pronouncement that the patient was deceased had to be reversed. The emotional relatives refused organ donation. In the second case, death was pronounced upon loss of consciousness and absence of brain stem reflexes. The relatives refused organ donation, after which mechanical ventilation was withdrawn and the patient was declared dead for a second time based on circulatory arrest. CONCLUSION: A patient is dead after complete brain death determination or after circulatory arrest. Loss of consciousness (Glasgow Coma score of 3) and absence of brain stem reflexes lead to a state of catastrophic cerebral damage, but not to brain death. In such a situation, wording such as 'brain death', 'deceased' and 'clinical brain death' should be avoided in conversations with the relatives.

INTRODUCTION: Intensive care is generally regarded as expensive, and as a result beds are limited. This has raised serious questions about rationing when there are insufficient beds for all those referred. However, the evidence for the cost effectiveness of intensive care is weak and the work that does exist usually assumes that those who are not admitted do not survive, which is not always the case. Randomised studies of the effectiveness of intensive care are difficult to justify on ethical grounds; therefore, this observational study examined the cost effectiveness of ICU admission by comparing patients who were accepted into ICU after ICU triage to those who were not accepted, while attempting to adjust such comparison for confounding factors. METHODS: This multi-centre observational cohort study involved 11 hospitals in 7 EU countries and was designed to assess the cost effectiveness of admission to intensive care after ICU triage. A total of 7,659 consecutive patients referred to the intensive care unit (ICU) were divided into those accepted for admission and those not accepted. The two groups were compared in terms of cost and mortality using multilevel regression models to account for differences across centres, and after adjusting for age, Karnofsky score and indication for ICU admission. The analyses were also stratified by categories of Simplified Acute Physiology Score (SAPS) II predicted mortality (< 5%, 5% to 40% and >40%). Cost effectiveness was evaluated as cost per life saved and cost per life-year saved. RESULTS: Admission to ICU produced a relative reduction in mortality risk, expressed as odds ratio, of 0.70 (0.52 to 0.94) at 28 days. When stratified by predicted mortality, the odds ratio was 1.49 (0.79 to 2.81), 0.7 (0.51 to 0.97) and 0.55 (0.37 to 0.83) for <5%, 5% to 40% and >40% predicted mortality, respectively. Average cost per life saved for all patients was $103,771 (euro82,358) and cost per life-year saved was $7,065 (euro5,607). These figures decreased substantially for patients with predicted mortality higher than 40%, $60,046 (euro47,656) and $4,088 (euro3,244), respectively. Results were very similar when considering three-month mortality. Sensitivity analyses performed to assess the robustness of the results provided findings similar to the main analyses. CONCLUSIONS: Not only does ICU appear to produce an improvement in survival, but the cost per life saved falls for patients with greater severity of illness. This suggests that intensive care is similarly cost effective to other therapies that are generally regarded as essential.

PURPOSE: To illustrate the impact on the validity of trial results due to excluding patients from a randomized controlled trial for whom no deferred consent could be obtained after randomization because study procedures had already been finished. METHODS: The unadjusted and adjusted primary outcome measures of a recent randomized controlled multicentre study in the field of intensive care medicine were compared, including (n = 348) or excluding (n = 289) patients with missing deferred consent. RESULTS: Thirty-nine patients (11%) died early, before the patient or his/her proxy could be approached and consent be obtained. In another 20 patients (6%), it was not possible to inform proxies and ask consent within the period of study procedures. A significant treatment effect (p = 0.006) in the adjusted analysis became non-significant (p = 0.35) when the patients with missing deferred consent were excluded. CONCLUSIONS: Exclusion of patients without obtained deferred consent can reduce statistical power, introduce selection bias, make randomization asymmetrical, decrease external validity and thereby jeopardize study results. This may have implications for emergency research in various disciplines.

RATIONALE: It is unknown whether lactate monitoring aimed to decrease levels during initial treatment in critically ill patients improves outcome. OBJECTIVES: To assess the effect of lactate monitoring and resuscitation directed at decreasing lactate levels in intensive care unit (ICU) patients admitted with a lactate level of greater than or equal to 3.0 mEq/L. METHODS: Patients were randomly allocated to two groups. In the lactate group, treatment was guided by lactate levels with the objective to decrease lactate by 20% or more per 2 hours for the initial 8 hours of ICU stay. In the control group, the treatment team had no knowledge of lactate levels (except for the admission value) during this period. The primary outcome measure was hospital mortality. MEASUREMENTS AND MAIN RESULTS: The lactate group received more fluids and vasodilators. However, there were no significant differences in lactate levels between the groups. In the intention-to-treat population (348 patients), hospital mortality in the control group was 43.5% (77/177) compared with 33.9% (58/171) in the lactate group (P = 0.067). When adjusted for predefined risk factors, hospital mortality was lower in the lactate group (hazard ratio, 0.61; 95% confidence interval, 0.43-0.87; P = 0.006). In the lactate group, Sequential Organ Failure Assessment scores were lower between 9 and 72 hours, inotropes could be stopped earlier, and patients could be weaned from mechanical ventilation and discharged from the ICU earlier. CONCLUSIONS: In patients with hyperlactatemia on ICU admission, lactate-guided therapy significantly reduced hospital mortality when adjusting for predefined risk factors. As this was consistent with important secondary endpoints, this study suggests that initial lactate monitoring has clinical benefit. Clinical trial registered with www.clinicaltrials.gov (NCT00270673).

PURPOSE: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. METHODS: We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. RESULTS: A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E(0)M(0)B(0)R(0). CONCLUSION: The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis.

BACKGROUND: The incidence of methanol (CH3OH) intoxication differs enormously from country to country. Methanol intoxication is extremely rare in the Dutch population. Even a low dose can already be potentially lethal. Patients are conventionally treated with hemodialysis. Therefore we'd like to present a report of a foreign sailor in Rotterdam who accidentally caused himself severe methanol intoxication, with a maximum measured concentration of 4.4 g/L. CASE PRESENTATION: The patient presented with hemodynamic instability and severe metabolic acidosis with pH 6.69. The anion gap was 39 mmol/L and the osmol gap 73 mosmol/kg. Treatment with ethanol and continuous venovenous hemodiafiltration (CVVH-DF) was initiated. Despite the hemodynamic instability it is was possible to achieve rapid correction of pH and methanol concentration with CVVH-DF while maintaining a stable and therapeutic ethanol serum concentration. Despite hemodynamic and acid-base improvement, our patient developed massive cerebral edema leading to brain death. Permission for organ donation was unfortunately not ascertained. CONCLUSIONS: We conclude that in a hemodynamic instable situation high methanol concentrations and methanol-induced derangements of homeostasis are safely and effectively treated with CVVH-DF and that severe cerebral edema is another possible cause of death rather than the classical bleeding in the putamen area.