C. P. Stoutenbeek

Systematic review of early prediction of poor outcome in anoxic- ischaemic coma

BACKGROUND Studies to assess the prognostic value of early neurological and neurophysiological findings in patients with anoxic-ischaemic coma have not led to precise, generally accepted, prognostic rules. We did a systematic review of the relevant literature to assess whether such rules could be derived from the combined results of these studies. METHODS From Medline and Embase databases we selected studies concerning patients older than 10 years with anoxic-ischaemic coma in which findings from early neurological examination, electroencephalogram (EEG), or somatosensory evoked potentials (SSEP) were related to poor outcome--defined as death or survival in a vegetative state. We selected variables with a specificity of 100% for poor outcome in all studies, and expressed the overall prognostic accuracy of these variables as pooled positive-likelihood ratios and as 95% CIs of the pooled false-positive test rates. FINDINGS In 33 studies, 14 prognostic variables were studied, three of which had a specificity of 100%: absence of pupillary light reflexes on day 3 (pooled positive-likelihood ratio 10.5 [95% CI 2.1-52.4]; 95% CI pooled false-positive test rate 0-11.9%); absent motor response to pain on day 3 (16.8 [3.4-84.1]; 0-6.7%); and bilateral absence of early cortical SSEP within the first week (12.0 [5.3-27.6]; 0-2.0%). EEG recordings with an isoelectric or burst-suppression pattern had a specificity of 100% in five of six relevant studies (pooled positive-likelihood ratio 9.0 [2.5-33.1]; 95%CI pooled false-positive test rate 0.2-5.9%). These characteristics were present in 19%, 31%, 33%, and 33% of pooled patient populations, respectively. For the 11 SSEP studies, results did not significantly differ between studies in which the treating physicians were or were not masked from the test result, prospective and retrospective studies, studies with short and long follow-up periods, and studies with high or low overall poor outcome. INTERPRETATION SSEP has the smallest CI of its pooled positive-likelihood ratio and its pooled false-positive test rate. Because evoked potentials are also the least susceptible to metabolic changes and drugs, recording of SSEP is the most useful method to predict poor outcome.

Intestinal permeability, circulating endotoxin, and postoperative systemic responses in cardiac surgery patients

OBJECTIVES To determine whether intestinal permeability increases during cardiac operations, and whether the degree of endotoxemia is related to this increase. Furthermore, to determine whether intestinal permeability is related to the hemodynamic state during operation and to postoperative systemic responses. DESIGN Prospective study. SETTING University hospital. PARTICIPANTS Twenty-three male patients undergoing elective coronary artery bypass surgery. INTERVENTIONS Before surgery and during the fifth postoperative day, 100 mL of a solution containing L-rhamnose and cellobiose were administered orally. MEASUREMENTS AND MAIN RESULTS Intestinal permeability was assessed by measuring the urinary excretion of L-rhamnose and cellobiose. Endotoxin concentrations in blood and prime fluid, hemodynamics, oxygen consumption, gas exchange, fluid balance, and the dose of vasoactive drugs were measured. Systemic responses were assessed by measuring hypermetabolism, circulatory support, and gas exchange. Intestinal permeation of cellobiose, reflecting paracellular transport, significantly increased during operation (p < 0.01), and correlated with the amount of circulating endotoxin (r2 = 0.46; p < 0.01). A high dose of ephedrine administered during operation, low baseline central venous pressure, and a less positive fluid balance during operation were associated with high intestinal permeability (r2 = 0.7; p < 0.01). Intestinal permeability was related to postoperative systemic responses (r2 = 0.49; p < 0.01). CONCLUSIONS This study shows that during elective coronary artery bypass operations intestinal permeability between cells may increase. The degree of endotoxemia is related to this increase. Increased intestinal permeability is related to the use of ephedrine, especially during hypovolemia, and to postoperative systemic responses. Although a causative relation is not shown, these results might indicate that hypovolemia and vasoconstriction should be avoided during the operation.

Current Drug Treatment Strategies for Disseminated Intravascular Coagulation

SummaryDisseminated intravascular coagulation (DIC) can be caused by a variety of diseases. Experimental models of DIC have provided substantial insight into the pathogenesis of this disorder, which may ultimately result in improved treatment. Disseminated coagulation is the result of a complex imbalance of coagulation and fibrinolysis. Simultaneously occurring tissue factor-dependent activation of coagulation, depression of natural anticoagulant pathways and shutdown of endogenous fibrinolysis all contribute to the clinical picture of widespread thrombotic deposition in the microvasculature and subsequent multiple organ failure.Cornerstone for the treatment of DIC is the optimal management of the underlying disorder. At present, specific treatment of the coagulation disorders themselves is not based on firm evidence from controlled clinical trials. Plasma and platelet transfusion are used in patients with bleeding or at risk for bleeding and low levels of coagulation factors or thrombocytopenia. The role of heparin and low molecular weight heparin is controversial, but their use may be justified in patients with active DIC and clinical signs of extensive fibrin deposition such as those with meningococcal sepsis. There is some evidence to indicate that low molecular weight heparin is as effective as unfractionated heparin but may be associated with a decreased bleeding risk.Antithrombin III (AT III) replacement appears to be effective in decreasing the signs of DIC if high doses are administered, but effects on survival or other clinically significant parameters are at best uncertain. If AT III supplementation is used, the dosage should be selected to achieve normal or supranormal plasma levels of 100% or higher. Results of studies on protein C concentrate, thrombomodulin or inhibitors of tissue factor are promising, but the efficacy and safety of these novel strategies remains to be established in appropriate clinical trials.

Thoracic Duct in Patients With Multiple Organ Failure: No Major Route of Bacterial Translocation

OBJECTIVE To determine whether translocation of bacteria or endotoxin occurred into the thoracic duct in patients with multiple organ failure (MOF). SUMMARY BACKGROUND DATA Translocation of bacteria or endotoxin has been proposed as a causative factor for MOF in patients without an infectious focus, although it has rarely been demonstrated in patients at risk for MOF. Most studies have investigated the hematogenic route of translocation, but it has been argued that lymphatic translocation of bacteria or endotoxin by the thoracic duct is the major route of translocation. METHODS The thoracic duct was drained for 5 days in patients with MOF caused either by generalized fecal peritonitis (n = 4) or by an event without clinical and microbiologic evidence of infection (n = 4). Patients without MOF who were undergoing a transthoracic esophageal resection served as controls. In lymph and blood, concentrations of endotoxin, proinflammatory cytokines, and antiinflammatory cytokines were measured. RESULTS Endotoxin concentrations in lymph and blood of patients with MOF ranged from 39 to 63 units per liter and were not significantly different from concentrations in patients without MOF. The quantity of endotoxin transported by the thoracic duct in the study group was small. In patients with MOF, low levels of proinflammatory cytokines and high levels of antagonists of these cytokines were found. CONCLUSION This study provides evidence that translocation (especially of endotoxin) occurs into the thoracic duct. However, these data do not support the concept that the thoracic duct is a major route of bacterial translocation in patients with MOF.

Increased oxygen consumption after cardiac surgery is associated with the inflammatory response to endotoxemia.

ObjectiveThe aim of this study was to determine whether the increase in post-operative oxygen consumption (ΔVO2) in cardiac surgery patients in related to endotoxemia and subsequent cytokine release and whether ΔVO2 can be used as a parameter of post-perfusion syndrome.DesignProspective study.SettingOperating room and intensive care unit of a university hospital.PatientsTwenty-one consecutive male patients undergoing elective coronary artery bypass surgery without major organ dysfunction and not receiving corticosteroids.Measurements and resultsPlasma levels of endotoxin, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were measured before, during and for 18 h after cardiac surgery. Oxygen consumption, haemodynamics, the use of IV fluids and dopamine, body temperature and the time of extubation were also measured. Measurements from patients with high ΔVO2 (≥median value of the entire group) were compared with measurements from patients with low ΔVO2 (<median). Patients with high ΔVO2 had higher levels of circulating endotoxin (P=0.004), TNF (P=0.04) and IL-6 (P=0.009) received more IV fluids and dopamine while in the ICU, and were extubated later than patients with low ΔVO2. Several hours after ΔVO2 the patients body temperature rose, Forward stepwise regression analysis showed that circulating endotoxin and TNF explained 50% of the variability of ΔVO2.ConclusionsThis study demonstrates that patients with high post operative oxygen comsumption after elective cardiac surgery have higher circulating levels of endotoxin, TNF and IL-6 and also have more symptoms of post-perfusion syndrome. Early detection of high VO2 might be used as a clinical signal to improve circulation in order to meet the high oxygen demand of inflammation. In addition, continuous measurement of VO2 provides us with a clinical parameter of inflammation in interventional studies aiming at a reduction of endotoxemia or circulating cytokines.

Analysis of P50 and oxygen transport in patients after cardiac surgery

ObjectiveTo determine whether standard P50 after cardiac surgery decreases and whether decreased P50 is related to the transfusion of red blood cells (RBCs), acid-base changes, body temperature, oxygen parameters and/or duration of cardiopulmonary bypass (CPB).DesignPilot study in cardiac surgery patients.SettingUniversity hospital.Patients12 consecutive elective cardiac surgery patients.InterventionsBlood was taken before surgery, after CPB and in the intensive care unit until 18 h post-operatively. Cardiac output and oxygen consumption were measured. Buffy coat-poor RBCs were transfused, anticoagulated with citratephosphate-dextrose buffer and stored in saline-adenine-glucose-mannitol at 4°C, when haemoglobin was <5.6 mmol·l−1.Measurements and resultsStandard P50 was calculated from measured partial pressure of oxygen and of carbon dioxide, pH and oxygen saturation in mixed venous blood (SvO2) using the Severinghaus formula. Median length of RBC storage was 25 days. Standard P50 after surgery was significantly lower than baseline value (p=0.0001). The number of RBC units transfused and duration of CPB were conjointly associated with P50 (R2=0.72). Patients who received more RBCs consumed more oxygen.ConclusionCardiac surgery patients receiving more RBC units have lower standard P50 and consume more oxygen. P50 decreased more when the CPB took longer. Because a decrease in P50 implies a low ratio of mixed venous oxygen tension (PvO2) to SvO2, a shift in P50 should be taken into account when using SvO2 as a measure of global oxygen availability. When a direct measurement of SvO2 is not available, PvO2 should be used instead of calculated SvO2.

Prevention of the Postperfusion Syndrome After Cardiopulmonary Bypass

The postoperative period following cardiopulmonary bypass (CPB) is often complicated by a clinical picture resembling septic shock. Most frequently it occurs in a mild form characterized by hyperthermia, marked peripheral vasoconstriction, hypotension, a normal or high cardiac output with a low peripheral vascular resistance.

Pathogenesis of Stress Ulcer Bleeding in the Critically Ill

The critically ill patient is at risk of developing erosive gastric and intestinal mucosal ulcerations which may finally cause bleeding. The incidence of ulcer bleeding in critically ill patients reported in the literature varies from 1 to 100%. This variation may be explained by differences in the underlying disease. Zinner and co-workers found evidence of ulcer-related bleeding in 1–11% of patients with minor critical illness but up to 100% in patients with severe critical illness [37].