Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear.Objectives: This study aimed to determine whether a low-oxygenation... Show moreRationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear.Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy.Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (Pa-O2, 55-80mmHg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (Pa-O2, 110-150mmHg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included.Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved Pa-O2 was 75mmHg (interquartile range, 70-84) and 115mmHg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively.Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Show less
Background: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen... Show moreBackground: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands.Methods: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios.Results: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO(2)) of 85-90% as acceptable for 15 minutes, and a PaO2 7-To kPa (53-75 mmHg) and SaO(2) 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO(2)) if SaO(2) was 90-95% or PaO2 was 12 kPa (90 mmHg).Conclusion: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO(2) targets in the lower physiological range and would adjust ventilation settings accordingly. Show less
Objective. The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis... Show moreObjective. The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis evaluating the effects of (individual) NMDA receptor antagonists on neuropathic pain, and the response (sensitivity) of individual neuropathic pain disorders to NMDA receptor antagonist therapy. Design. PubMed (including MEDLINE), EMBASE and CENTRAL were searched up to October 26, 2009 for randomized placebo controlled trials (RCTs) on neuropathic pain. The methodological quality of the included trials was independently assessed by two authors using the Delphi list. Fixed or random effects model were used to calculate the summary effect size using Hedges' g. Setting. NA. Patients. The patients used for the study were neuropathic pain patients. Interventions. The interventions used were NMDA receptor antagonists. Outcome measurements. The outcome of measurements was the reduction of spontaneous pain. Results. Twenty-eight studies were included, meeting the inclusion criteria. Summary effect sizes were calculated for subgroups of studies evaluating ketamine IV in complex regional pain syndrome (CRPS), oral memantine in postherptic neuralgia and, respectively, ketamine IV, and oral memantine in postamputation pain. Treatment with ketamine significantly reduced pain in postamputation pain (pooled summary effect size: -1.18 [confidence interval (CI) 95% -1.98, -0.37], P=0.004). No significant effect on pain reduction could be established for ketamine IV in CRPS (-0.65 [CI 95% -1.47, 0.16], P=0.11) oral memantine in postherptic neuralgia (0.03 [CI 95% -0.51, 0.56], P=0.92) and for oral memantine in postamputation pain (0.38 [Cl 95% -0.21,0.98], P=0.21). Conclusions. Based on this systematic review, no conclusions can yet be made about the efficacy of NMDA receptor antagonists on neuropathic pain. Additional RCTs in homogenous groups of pain patients are needed to explore the therapeutic potential of NMDA receptor antagonists in neuropathic pain. Show less
Chronic pain is a widespread condition in the general population. For this reason, chronic pain management has received increased attention in recent years, both in clinical practice and in... Show moreChronic pain is a widespread condition in the general population. For this reason, chronic pain management has received increased attention in recent years, both in clinical practice and in scientifi c research. This thesis describes a series of experiments which studied the effi cacy and safety of ketamine in subanesthetic doses. Both healthy volunteers and chronic pain patients were recruited for these studies. The specifi c chronic pain condition studied in these experiments was Complex Regional Pain Syndrome type 1, which is characterized by chronic pain affecting one or more extremities. It is very diffi cult to treat this condition with current pharmacotherapeutic interventions. However, one of the studies in this thesis showed that a continuous ketamine infusion, lasting for several days, can have a prolonged effect in reducing pain scores for up to several weeks (despite rapidly decreasing ketamine plasma concentrations after termination of the infusion). In addition, experiments in both healthy volunteers and patients were performed to study the pharmacokinetics and pharmacodynamics of ketamine in subanesthetic doses. Show less
