Marc Diltoer

Gastric emptying in critically ill patients is accelerated by adding cisapride to a standard enteral feeding protocol : results of a prospective, randomized controlled trial

OBJECTIVE To investigate the effect of cisapride, a relatively new prokinetic agent, on gastric emptying in critically ill patients. DESIGN Prospective, randomized, controlled study. SETTING Adult medical/surgical intensive care unit in a university hospital. PATIENTS Twenty-one consecutively enrolled patients, requiring prolonged mechanical ventilation and enteral feeding. INTERVENTIONS Patients were randomized to receive either no cisapride or 10 mg of cisapride four times daily, which was added to a standard enteral nutrition feeding protocol. MEASUREMENTS AND MAIN RESULTS Gastric emptying was evaluated by daily measurements of gastric residue and on days 5 through 7 by bedside scintigraphy. Normal values for gastric clearance of a tracer-labeled test meal and for measurements obtained in the supine position were determined in ten healthy volunteers. The mean time at which 50% of the technetium 99m-labeled test meal was eliminated from the stomach (T 1/2) in this control group was 31 +/- 15 mins. In ten critically ill patients (enteral nutrition group), gastric emptying was markedly delayed after 5 to 7 days of enteral feeding (mean T 1/2 = 78 +/- 40 mins; p < .002 as compared with the control group). In contrast, patients treated with cisapride (cisapride group) showed an accelerated gastric emptying (mean T 1/2 = 18 +/- 7 mins; p > .05 as compared with controls; p < .005 as compared with enteral nutrition group). The mean gastric residue over a 1-wk period was also significantly lower in the cisapride group than in the enteral nutrition group (17.7 +/- 8.9 vs. 94.5 +/- 33.4 mL; p < .001). CONCLUSIONS The data indicate that gastric emptying in critically ill, sedated, and mechanically ventilated patients can be significantly improved by adding cisapride to a routine enteral feeding protocol.

Effects of N-acetylcysteine on Microalbuminuria and Organ Failure in Acute Severe Sepsis : Results of a Pilot Study

STUDY OBJECTIVE The level of microalbuminuria is thought to reflect the severity of inflammation-induced systemic vascular permeability and may have prognostic value with regard to organ dysfunction and survival. N-acetylcysteine (NAC) has been shown to decrease capillary leakage in experimental sepsis. The present study investigated the effect of early treatment with NAC on microalbuminuria and organ dysfunction in severe clinical sepsis. DESIGN Prospective, randomized, placebo-controlled study. SETTING A 24-bed multidisciplinary ICU in a university teaching hospital. PATIENTS Thirty-five patients included within 4 h of fulfilling consensus criteria of severe sepsis. INTERVENTIONS Patients were randomly assigned to receive either NAC (continuous infusion starting with 50 mg/kg/4 h followed by 100 mg/kg/24 h for 44 h; n = 18) or placebo (n = 17) in addition to standard therapy. MEASUREMENTS AND RESULTS Urine samples for measurement of microalbuminuria/creatinine ratio (MACR) were collected on inclusion and after 4 h, 24 h, and 48 h. Severity of illness and degree of organ failure were determined by using, respectively, the APACHE (acute physiology and chronic health evaluation) II score and the sequential organ failure assessment (SOFA) score. The MACR did not differ over time between the placebo- and the NAC-treated groups. SOFA scores were comparable between both treatment groups at baseline (6.2 +/- 3.9 vs 6.5 +/- 2.7, NAC vs placebo; p = 0.6) and increased during treatment in the NAC-treated patients but not in the placebo group (7.9 +/- 3.7 vs 5.9 +/- 2.5, p = 0.09 and 7.7 +/- 3.8 vs 5.1 +/- 2.1, p < 0.05; NAC vs placebo, respectively, at 24 h and at 48 h). The cardiovascular SOFA score progressively increased during NAC treatment, reaching higher values as compared to time-matched scores in the placebo group. CONCLUSIONS Early NAC administration does not influence the course of MACR in severe clinical sepsis, suggesting that NAC might not attenuate endothelial damage in this condition. NAC treatment even aggravated sepsis-induced organ failure, in particular cardiovascular failure.

Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients : Results of a randomized, double-blind, placebo-controlled trial

Objective:To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. Design:Randomized, double-blind, placebo-controlled study. Setting:Medical, surgical, or mixed medical/surgical intensive care units. Patients:A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. Interventions:Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n = 48) or matching placebo (n = 25) for up to 4 wks. Measurements and Main Results:Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. Conclusion:Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.

Liver perfusion and hepatocellular inflammatory response in sepsis.

Sepsis is characterized by disturbances in liver perfusion and alterations in intrahepatic cellular functions and interactions. This provokes structural and functional liver damage as well as hepatocellular activation that is believed to perpetuate the immuno-inflammatory response. Changes in hepatic perfusion during sepsis are still poorly understood due to the heterogeneity of septic animal models and the difficult accessibility of the hepatic circulation in humans. Sinusoidal blood flow is severely compromised during sepsis due to a decline in perfused sinusoidal area in association with a decrease in sinusoidal flow velocity. Imbalances in the production of nitric oxide may account for these (micro) circulatory disorders. Interactions between liver macrophages, activated endothelial cells and hepatocytes determine the intensity of inflammation and contribute to initial liver damage. Hepatocellular injury is then enhanced by attracted and invading neutrophils. The management of hepatic dysfunction during sepsis is largely supportive and based on prevention and vigorous resuscitation including early nutritional support and adequate oxygenation. Interestingly, experimental studies suggest that pharmacological interventions with significant hemodynamic effects, such as dobutamine and nitric oxide synthase inhibitors, may adversely affect the liver during the septic process.

Measuring resting energy expenditure during extracorporeal membrane oxygenation: preliminary clinical experience with a proposed theoretical model.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe respiratory failure. Indirect calorimetry (IC) is a safe and non‐invasive method for measuring resting energy expenditure (REE). No data exist on the use of IC in ECMO‐treated patients as oxygen uptake and carbon dioxide elimination are divided between mechanical ventilation and the artificial lung. We report our preliminary clinical experience with a theoretical model that derives REE from IC measurements obtained separately on the ventilator and on the artificial lung.

Anticholinergic Treatment for Choreoathetosis in a Child After Induction with Propofol

We present a case of extrapyramidal side effects during administration of induction of anesthesia dose of propofol in a child and their treatment. A boy, 7 yr old, was admitted to the pediatric intensive care unit for supraventricular tachycardia. He had been electrically cardioverted previously using etomidate. No premeditation was given. During intravenous (IV) administration of propofol, he complained of pain on the injection site. This was accompanied by movements of the head, arms, and legs. After a dose of 3 mg/kg, the patient became unconscious and required mechanical ventilation via mask. He presented involuntary movements of the four limbs in a violent twisting motion, which necessitated restraining. A few minutes later, the movements were dystonic and choreiform with flexion, twist, or extension of the arms or legs. They were most often bilateral but not strictly symmetric. No trismus was present. No urine loss was observed. The dose of propofol was increased to 4 mg/kg, without changing the involuntary movements. The subsequent titrated administration of 18 mg etomidate did not alter these movements. Since the body motion hindered the safe performance of external electrical cardioversion, succinylcholine 25 mg IV was given. Once paralyzed, 30 joules were administered and prompt sinus rhythm occurred. Three minutes later, the extrapyramidal signs reappeared while the patient was unconscious and still required controlled ventilation. Biperiden 1 mg was slowly given IV. The movements disappeared within a few minutes. The patient regained spontaneous breathing and consciousness without any further adverse effects. He did not report (un)pleasant dreams or any awareness during the procedure. A higher incidence of spontaneous movements during induction of anesthesia with propofol was observed in children compared with adults (1,2). In seven out of seven children, Borgeat et al. (2) found spontaneous movements after induction with propofol (3 mg/kg followed by 0.1 mg . kg-’ * mini). These movements showed interindividual differences in intensity and lasted less than 50 s. The dystonic and choreiform nature of these movements and the absence of electroencephalographic abnormalities suggested a subcortical origin. In the above case, the involuntary movements lasted for several minutes and were successfully controlled by the injection of the anticholinergic drug. The latter suggests an effect of propofol at the level of the basal ganglia, where an imbalance between the cholinergic and dopaminergic activity can induce acute idiosyncratic dyskinesia including choreoathetosis. We did not observe a beneficial effect of increasing the dose from 3 to 4 mg/kg, although it was demonstrated that increasing the dose of propofol (to 5 mg/kg) reduces the incidence of the involuntary movements at induction (2). Excitatory adverse effects (including seizures) of propofol are known (3,4) and rare (5). Ries et al. (3) discussed the treatment strategy for nonepileptic excitatory events such as opisthotonos suggesting the use of diazepam or physostigmine to restore the neuronal inhibition by glycine and y-aminobutyric acid to counteract these phenomena. In this case, neither opisthotonos nor tonic-clonic movements were present and administration of etomidate, increasing GABA-ergic inhibitory action, did not alter the clinical presentation. We conclude that an induction dose of propofol may induce choreoathetosis-like movements in children, which in rare cases may be severe and may last for several minutes, possibly leading to physical harm if the patient is not restrained. Treatment with an anticholinergic drug can quickly result in the disappearance of this side effect.

Citrate Formulation Determines Filter Lifespan during Continuous Veno-Venous Hemofiltration: A Prospective Cohort Study

Introduction: We conducted an 8-month prospective single-center observational study in patients with acute kidney injury treated with continuous veno-venous hemofiltration (CVVH) to compare the impact of two citrate formulations on filter lifespan (FLS). Methods: Patients received CVVH at a delivered dose of 25 ml/kg/h. Multivariable linear regression was performed to assess the influence of different variables on circuit lifespan. Results: We included 59 patients, 28 received the 10/2 formulation and 31 received the 18/0 formulation. Median (interquartile range) FLS was significantly prolonged with the 18/0 solution compared with the 10/2 solution (4.10 (2.45-5.75) vs. 2.68 (0.47-4.99) days, p = 0.001). No confounding variables (difference in ionized calcium target, citrate flow or dose, platelet count, hematocrit, vascular access location) affecting filter capacity or lifespan between the 2 formulations were identified. Conclusions: Under similar conditions of CVVH and calcium targets, a Prismocitrate 18/0 formulation significantly improved FLS as compared with Prismocitrate 10/2.

DO-NOT-RESUSCITATE ORDERS IN THE CRITICALLY ILL PATIENT - AN OBSERVATIONAL STUDY WITH SPECIAL EMPHASIS ON WITHHOLDING OF RENAL REPLACEMENT THERAPY

Abstract We examined the process, consequences and impact of writing a Do-Not-Resuscitate (DNR) order in a cohort of critically-ill ICU patients. Special emphasis was given to the DNR order including withholding renal replacement therapy. A DNR code was mainly written in the first week following ICU admission and more often given to medical, older and sicker patients. Patients never actively participated in the decision and in only half of the cases the DNR order was discussed with relatives. Mortality of all patients studied was 21% of whom 67% died with a DNR order. In our population, the final in-hospital mortality rate of DNR-coded patients was 100%, because the DNR status was ordered when the patients were already very sick. DNR-coded patients died after a longer mean length of ICU stay than patients without a code. Withholding renal replacement therapy was commonly added to the DNR order even if renal failure either was not present or never developed.

Passive immunotherapy of Gram-negative bacteremia, sepsis and septic shock

Despite the use of increasingly potent antibiotics and aggressive cardiovascular monitoring and support, Gram-negative bacteremia and ensuing sepsis and septic shock remain a leading cause of morbidity and mortality after surgery and in critically ill patients. In previous years several new agents and techniques have been developed to improve management and outcome of severe Gram-negative infections. A recently introduced treatment is passive immunotherapy by administration of poly- or monoclonal anti-endotoxin antibodies. The current view--sustained by experimental and human studies--on the mechanism of protection afforded by immunotherapy is that the harmful effects of endotoxin are neutralized by cross-reactive antibodies to the core glycolipid structure of rough mutant Gram-negative bacilli. Two recent large clinical trials reported impressive results achieved through the use of monoclonal anti-endotoxin antibodies in certain subgroups of patients with Gram-negative sepsis. However, this treatment is empirical, expensive and it does not affect overall sepsis mortality. Cytokines such as tumor necrosis factor alpha and interleukin-1 play a pivotal role in sepsis. Experimental studies suggest that specific antagonism of these mediators might offer great perspectives for the treatment of Gram-negative sepsis. An early multi-pharmacological approach aimed at interruption of multiple steps underlying the inflammatory septic cascade will probably constitute the most promising future treatment of severe Gram-negative infectious disease.

High-frequency percussive ventilation in severe acute respiratory distress syndrome: A single center experience

Background: Few studies have investigated high-frequency percussive ventilation (HFPV) in adult patients with acute respiratory distress syndrome (ARDS). Materials and Methods: We retrospectively analyzed data from critically ill-patients with moderate and severe ARDS who received HFPV. Ventilation and oxygenation were governed according to a predefined protocol. HFPV was continued until patients could be switched to conventional ventilation. Results: A total of 42 patients (20 with pneumonia-related ARDS and 22 non-septic ARDS cases) were evaluable. Baseline demographic characteristics, severity of illness, lung injury score; pH and respiratory variables were comparable between pneumonia and non-sepsis-related ARDS. Within 24 h, HFPV restored normal pH and PaCO2 and considerably improved oxygenation. Oxygenation improved more in non-septic than in pneumonia-related ARDS. Patients with pneumonia-induced ARDS also remained longer HFPV-dependent (7.0 vs. 4.9 days; P < 0.05). Mortality at 30 days was significantly higher in pneumonia-related than in non-sepsis-related ARDS (50% vs. 18%; P = 0.01). Conclusions: HFPV caused rapid and sustained improvement of oxygenation and ventilation in patients with moderate to severe ARDS. Less improved oxygenation, longer ventilator dependency and worse survival were observed in pneumonia-related ARDS.