Phosphodiesterase 3 inhibitors do not influence lactate kinetics and clinical outcomes in patients with septic shock: A multicentre cohort study.

PURPOSE: We investigated the association between the administration of phosphodiesterase 3 inhibitors (PDE3i) and lactate kinetics, resolution of organ failure, ICU and hospital length of stay (LOS) and hospital mortality in a retrospective cohort of patients with septic shock and persistently elevated lactate concentrations. MATERIAL AND METHODS: Patients with septic shock and two arterial lactate concentrations ≥4 mmol/L with at least 4 h between measurements were eligible. Clinical data of the first four days of admission were collected in an online database. For each patient, the area between the actual lactate concentrations and 2.2 mmol/L (AUClact2.2), was calculated for three days. RESULTS: Data on 229 patients from 10 hospitals were collected, of whom 123 received PDE3i (54%). First, a linear multivariate model was developed to predict AUClact2.2 (R2 = 0.57). Adding PDE3i as a cofactor did not affect R2. Second, 60 patients receiving PDE3i at any time between days 0 and 2 were compared to 60 propensity matched no-PDE3i patients. Third, 30 patients who received PDE3i from ICU admission to day 3 were compared to 30 propensity-matched no-PDE3i patients. These analyses showed no differences in AUClact2.2, SOFA scores, ICU or hospital LOS or hospital mortality between treatment groups. CONCLUSIONS: No association was found between the administration of PDE3i and lactate kinetics, resolution of organ failure, ICU or hospital LOS or hospital mortality.

Feasibility of critical care ergometry: Exercise data of patients on mechanical ventilation analyzed as nine-panel plots.

Nine-panel plots are standard displays of cardiopulmonary exercise data, used in cardiac and pulmonary medicine to investigate the nature of exercise limitation. We explored whether this approach could be used to analyze the data of critically ill patients on mechanical ventilation, capable of exercising actively. Patients followed an incremental exercise protocol using a bedside cycle ergometer. Respiratory gases were analyzed using indirect calorimetry, and blood gases were sampled from arterial catheters. Data of seven patients were combined into nine-panel plots. Systematic analysis clarified the nature of exercise limitation in six cases. Resting metabolic rate was increased in all patients, with a median oxygen uptake ( V˙O2 ) of 5.52 (IQR 4.29-6.31) ml/kg/min. Unloaded cycling increased the V˙O2 by 19.8% to 6.61 (IQR 5.99-7.08) ml/kg/min. Adding load to the ergometer increased the V˙O2 by another 20.0% to reach V˙O2peak at a median of 7.14 (IQR 6.67-10.75) ml/kg/min, corresponding to a median extrinsic workload of 7 W. This was accompanied by increased CO2 production, respiratory minute volume, heart rate, and oxygen pulse. Three patients increased their V˙O2 to >40% of predicted V˙O2max , two patients passed the anaerobic threshold. Dead space ventilation was 44%, decreasing to 42% and accompanied by lower ventilatory equivalents during exercise. Exercise produced no net change in alveolo-arterial PO2 difference. We concluded that diagnostic ergometry in mechanically ventilated patients was feasible. Analysis of the data as nine-panel plots provided insight into individual limitations to exercise.

The performance of COBRA, a decision rule to predict the need for intensive care interventions in intentional drug overdose.

BACKGROUND: COBRA was developed as a decision rule to predict which patients visiting the emergency department (ED) following intentional drug overdose will not require intensive care unit (ICU) interventions. COBRA uses parameters from five vital systems (cardiac conduction, oxygenation, blood pressure, respiration, and awareness) that are readily available in the ED. COBRA recommends against ICU admission when all these parameters are normal. OBJECTIVE: The primary aim of this study was to determine the negative predictive value (NPV) of COBRA in predicting ICU interventions. Secondary outcomes were the sensitivity, specificity and positive predictive value (PPV), and the observation time required for a reliable prediction. DESIGN: Observational cohort study. SETTINGS AND PARTICIPANTS: Patients with a reported intentional overdose with drugs having potential acute effects on neurological, circulatory or ventilatory function were included, and data necessary to complete the decision rule was collected. The attending physician in the ED made the actual admission decision, on the basis of clinical judgement. COBRA was measured 0, 3 and 6 h after arrival at the ED. OUTCOME MEASURES: Need for ICU interventions (treatment of convulsion; defibrillation; mechanical or noninvasive ventilation; intravenous administration of vasopressive agents, antiarrhythmics, atropine, calcium, magnesium or sedation; continuous hemofiltration or administration of antagonist/antidote and fluid resuscitation). MAIN RESULTS: Of 230 new cases (144 unique patients), 59 were immediately referred to the psychiatric services and/or sent home by the attending physician, 27 went to a regular ward, and 144 were admitted to the ICU. Of these 144 cases, 40 required one or more ICU interventions. By the time the first parameters were collected, the NPV of COBRA was 95.6%. After 3 h of observation, NPV was 100%, while sensitivity, specificity and PPV were 100, 61.1 and 35.1%, respectively. None of these values improved by prolonging the observation time to 6 h. CONCLUSION: In patients with a reported intentional overdose with drugs having potential acute effects on neurological, circulatory or ventilatory function, the COBRA decision rule showed good performances in predicting the need for intensive care interventions, with a NPV of 100% after 3 h of observation.

Prevalence and management of delirium in intensive care units in the Netherlands: An observational multicentre study.

OBJECTIVES: This study aimed to determine the prevalence, risk factors of delirium and current practice of delirium management in intensive care units of various levels of care. RESEARCH METHODOLOGY/DESIGN: Prospective multicentre cohort study. SETTING: In all adult patients admitted to one of the participating intensive care units on World Delirium Awareness Day 2018, delirium point and period prevalence rates were measured between ICU admission and seven days after the index day. RESULTS: In total, 28 (33%) Dutch intensive care units participated in this study. Point-prevalence was 23% (range 41), and period-prevalence was 42% (range 70). University intensive care units had a significantly higher delirium point-prevalence compared with non-university units (26% vs.15%, p = 0.02). No significant difference were found in period prevalence (50% vs. 39%, p = 0.09). Precipitating risk factors, infection and mechanical ventilation differed significantly between delirium and non-delirium patients. No differences were observed for predisposing risk factors. A delirium protocol was present in 89% of the ICUs. Mean delirium assessment compliance measured was 84% (±19) in 14 units and estimated 59% (±29) in the other 14. CONCLUSION: Delirium prevalence in Dutch intensive care units is substantial and occurs with a large variation, with the highest prevalence in university units. Precipitating risk factors were more frequent in patients with delirium. In the majority of units a delirium management protocol is in place.

Optimising the dose of clonidine to achieve sedation in intensive care unit patients with population pharmacokinetics.

AIMS: The aim of this study was to investigate the population pharmacokinetics (PK) of clonidine in intensive care unit (ICU) patients in order to develop a dosing regimen for sedation. METHODS: We included 24 adult mechanically ventilated, sedated patients from a mixed medical and surgical ICU. Intravenous clonidine was added to standard sedation in doses of 600, 1200 or 1800 µg/d. Within each treatment group, 4 patients received a loading dose of half the daily dose administered in 4 hours. Patients gave an average of 12 samples per individual. In total, 286 samples were available for analysis. Model development was conducted with NONMEM and various covariates were tested. After modelling, doses to achieve a target steady-state plasma concentration of >1.5 µg/L were explored using stochastic Monte Carlo simulations for 1000 virtual patients. RESULTS: A 2-compartment model was the best fit for the concentration-time data. Clearance (CL) increased linearly with 0.213%/h; using allometric scaling, body weight was a significant covariate on the central volume of distribution (V1). Population PK parameters were: CL 17.1 (L/h), V1 124 (L/70 kg), intercompartmental CL 83.7 (L/h), and peripheral volume of distribution 178 (L), with 33.3% CV interindividual variability on CL and 66.8% CV interindividual variability on V1. Simulations revealed that a maintenance dose of 1200 µg/d provides target sedation concentrations of >1.5 µg/L in 95% of the patients. CONCLUSION: A population PK model for clonidine was developed in an adult ICU. A dosing regimen of 1200 µg/d provided a target sedation concentration of >1.5 µg/L.

In vivo Elimination of Clonidine by Continuous Venovenous Hemofiltration in Critically Ill Patients.

BACKGROUND: Clonidine is an α2-agonist that is commonly used for sedation in the intensive care unit. When patients are on continuous venovenous hemofiltration (CVVH) in the presence of kidney dysfunction, the sieving coefficient of clonidine is required to estimate how much drug is removed by CVVH. In the present study, we measured the sieving coefficient of clonidine in critically ill, ventilated patients receiving CVVH. METHODS: A total of 20 samples of plasma and ultrafiltrate of 3 patients on CVVH, using a standard 1.5 m2 polyacrylonitrile AN69 membrane, during continuous clonidine infusion were collected. After correction for the effect of predilution, we calculated the sieving coefficient for clonidine. RESULTS: The mean sieving coefficient of clonidine was 0.52 (SD 0.097). CONCLUSION: Using a polyacrylonitrile AN69 membrane in a CVVH machine, the in vivo sieving coefficient of clonidine was 0.52.

Feasibility of Exercise Testing in Patients Who Are Critically Ill: A Prospective, Observational Multicenter Study.

OBJECTIVE: To evaluate the feasibility and safety of exercise testing and to describe the physiological response to exercise of patients in the Intensive Care Unit (ICU). DESIGN: A prospective observational multicenter study. SETTING: Two mixed medical-surgical ICUs. PARTICIPANTS: Patients (N=37; with no primary neurological disorders, 59% men; median age 50y; ICU length of stay 14.5d; Acute Physiology and Chronic Health Evaluation IV 73.0) who had been mechanically ventilated for more than 48 hours and were hemodynamically stable enough to perform physical exercise. INTERVENTIONS: A passive or active incremental exercise test, depending on muscle strength, on a bed-based cycle ergometer. MAIN OUTCOME MEASURES: Feasibility and safety were evaluated based on protocol adherence and adverse events. Physiological responses to exercise quantified as changes in respiratory frequency (RF), oxygen uptake (Vo2), carbon dioxide output (Vco2), respiratory exchange ratio (RER), and blood lactate. RESULTS: Thirty-seven patients of whom 18 were mechanically ventilated underwent the exercise test. The active incremental test was performed by 28, and the passive test by 9 participants. Thirty-three (89%) accomplished the test according to the protocol and 1 moderate severe adverse event (bradycardia; heart rate 44) occurred shortly after the test. RF, Vo2, Vco2, and lactate increased significantly, whereas RER did not change during the active incremental exercise test. No changes were observed during the passive exercise test. CONCLUSIONS: It is safe and feasible to perform exercise testing on a bed-based cycle ergometer in patients who are critically ill and a physiological response could be measured. Future research should investigate the clinical value of exercise testing in daily ICU practice and whether exercise capacity and its limiting factors could be determined by incremental exercise testing.

Clinical parameters that predict the need for medium or intensive care admission in intentional drug overdose patients: A retrospective cohort study.

INTRODUCTION: Many patients with intentional drug overdose (IDO) are admitted to a medium (MC) or intensive care unit (IC) without ever requiring MC/IC related interventions. The objective of this study was to develop a decision tool, using parameters readily available in the emergency room (ER) for patients with an IDO, to identify patients requiring admission to a monitoring unit. METHODS: Retrospective cohort study among cases of IDO with drugs having potentially acute effects on neurological, circulatory or ventilatory function, admitted to the MC/IC unit between 2007 and 2013. A decision tool was developed, using 6 criteria, representing intubation, breathing, oxygenation, cardiac conduction, blood pressure, and consciousness. Cases were labeled as 'high acuity' if one or more criteria were present. RESULTS: Among 255 cases of IDO that met the inclusion criteria, 197 were identified as "high acuity". Only 70 of 255 cases underwent one or more MC/IC related interventions, of which 67 were identified as 'high acuity by the decision tool (sensitivity 95.7%). CONCLUSION: In a population of patients with intentional drug overdose with agents having potentially acute effect on vital functions, 95.7% of MC/IC interventions could be predicted by clinical assessment, supplemented with electrocardiogram and blood gas analysis, in the ER.

Orthogonal polarization spectral imaging of the microcirculation during acute hypervolemic hemodilution and epidural lidocaine injection.

We used Orthogonal Polarization Spectral Imaging to examine the microcirculation of the vaginal mucosa in nine anesthetized patients during two consecutive anesthetic interventions: hypervolemic hemodilution using hydroxyethyl starch followed by thoracic epidural lidocaine. Images taken before and after each intervention were compared. During hypervolemic hemodilution, systolic blood pressures increased significantly, but functional capillary density remained unchanged. Epidural anesthesia decreased systolic and diastolic blood pressures, but there was no change in capillary density, venular diameter, or flow velocity. We concluded that when using Orthogonal Polarization Spectral imaging, no consistent effects on the microcirculation of the vaginal wall can be detected.

Spinal anesthesia as a complication of brachial plexus block using the posterior approach.

IMPLICATIONS: In this case report we describe a technique used to provide local analgesia for surgical procedures. Although this technique has a reduced risk of complications, we present a patient who experienced a life-threatening paralysis without loss of consciousness during an attempted brachial plexus block with a posterior approach.