Günter Luckner

Macroscopic postmortem findings in 235 surgical intensive care patients with sepsis.

BACKGROUND: Although detailed analyses of the postmortem findings of various critically ill patient groups have been published, no such study has been performed in patients with sepsis. In this retrospective cohort study, we reviewed macroscopic postmortem examinations of surgical intensive care unit (ICU) patients who died from sepsis or septic shock. METHODS: Between 1997 and 2006, the ICU database and autopsy register were reviewed for patients who were admitted to the ICU because of sepsis/septic shock, or who developed sepsis/septic shock at a later stage during their ICU stay and subsequently died from of sepsis/septic shock. Clinical data and postmortem findings were documented in all patients. RESULTS: Postmortem results of 235 patients (84.8%) were available for statistical analysis. The main causes of death as reported in the patient history were refractory multiple organ dysfunction syndrome (51.5%) and uncontrollable cardiovascular failure (35.3%). Pathologies were detected in the lungs (89.8%), kidneys/urinary tract (60%), gastrointestinal tract (54%), cardiovascular system (53.6%), liver (47.7%), spleen (33.2%), central nervous system (18.7%), and pancreas (8.5%). In 180 patients (76.6%), the autopsy revealed a continuous septic focus. The most common continuous foci were pneumonia (41.3%), tracheobronchitis (28.9%), peritonitis (23.4%), uterine/ovarial necrosis (9.8% of female patients), intraabdominal abscesses (9.1%), and pyelonephritis (6%). A continuous septic focus was observed in 63 of the 71 patients (88.7%) who were admitted to the ICU because of sepsis/septic shock and treated for longer than 7 days. CONCLUSIONS: Relevant postmortem findings explaining death in surgical ICU patients who died because of sepsis/septic shock were a continuous septic focus in approximately 80% and cardiac pathologies in 50%. The most frequently affected organs were the lungs, abdomen, and urogenital tract. More diagnostic, therapeutic and scientific efforts should be launched to identify and control the infectious focus in patients with sepsis and septic shock.

Causes of death and determinants of outcome in critically ill patients

IntroductionWhereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients.MethodsThree thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods.ResultsAcute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively).ConclusionIn this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.

A Comparison of the Combination of Epinephrine and Vasopressin with Lipid Emulsion in a Porcine Model of Asphyxial Cardiac Arrest After Intravenous Injection of Bupivacaine

BACKGROUND:In a porcine model, we compared the effect of the combination of vasopressin/epinephrine with that of a lipid emulsion on survival after bupivacaine- induced cardiac arrest. METHODS:After administration of 5 mg/kg of a 0.5% bupivacaine solution IV, ventilation was interrupted for 2 ± 0.5 (mean ± sd) min until asystole occurred. Cardiopulmonary resuscitation (CPR) was initiated after 1 min of untreated cardiac arrest. After 2 min of CPR, 10 animals received, every 5 min, either vasopressin combined with epinephrine or 4 mL/kg of a 20% lipid emulsion. Three minutes after each drug administration, up to three countershocks (4, 4, and 6 J/kg) were administered; all subsequent shocks with 6 J/kg. Blood for determination of the plasma bupivacaine concentration was drawn throughout the experiment. RESULTS:In the vasopressor group, all five pigs survived, whereas none of five pigs in the lipid group had restoration of spontaneous circulation (P < 0.01). There was no significant difference between groups in the plasma concentration of total bupivacaine. CONCLUSION:In this model of a bupivacaine-induced cardiac arrest, the vasopressor combination of vasopressin and epinephrine compared with lipid emulsion resulted in higher coronary perfusion pressure during CPR and survival rates.

Serum vasopressin concentrations in critically ill patients.

Objective:To measure arginine vasopressin (AVP) serum concentrations in critically ill patients. Design:Prospective study. Setting:Twelve-bed general and surgical intensive care unit in a tertiary, university teaching hospital. Patients:Two-hundred-thirty-nine mixed critically ill patients and 70 healthy volunteers. Interventions:None. Measurements and Main Results:Demographic data, hemodynamic variables, vasopressor drug requirements, blood gases, AVP serum concentrations within 24 hrs after admission, multiple organ dysfunction score, and outcome were recorded. Twenty-four hours after admission, study patients had significantly higher AVP concentrations (11.9 ± 20.6 pg/mL) than healthy controls (0.92 ± 0.38 pg/mL; p < .001). Males had lower AVP concentrations than females (9.7 ± 19.5 vs. 15.1 ± 20.6 pg/mL; p = .014). Patients with hemodynamic dysfunction had higher AVP concentrations than patients without hemodynamic dysfunction (14.1 ± 27.1 vs. 8.7 ± 10.8 pg/mL; p = .042). Patients after cardiac surgery (n = 96) had significantly higher AVP concentrations when compared to patients admitted for other diagnoses (n = 143; p < .001). AVP concentrations were inversely correlated with length of stay in the intensive care unit (correlation coefficient, −0.222; p = .002). There was no correlation between serum AVP concentrations and the incidence of shock or specific hemodynamic parameters. Four (1.7%) of the 239 study patients met criteria for an absolute AVP deficiency (AVP, <0.83 pg/mL), and 32 (13.4%) met criteria for a relative AVP deficiency (AVP, <10 pg/mL, and mean arterial pressure, <70 mm Hg). In shock patients, relative AVP deficiency occurred in 22.2% (septic shock), 15.4% (postcardiotomy shock), and 10% (shock due to a severe systemic inflammatory response syndrome) (p = .316). Conclusions:AVP serum concentrations 24 hrs after intensive care unit admission were significantly increased in this mixed critically ill patient population. The lack of a correlation between AVP serum concentrations and hemodynamic parameters suggests complex dysfunction of the vasopressinergic system in critical illness. Relative and absolute AVP deficiency may be infrequent entities during acute surgical critical illness, mostly remaining without significant effects on cardiovascular function.

The vasopressin and copeptin response to infection, severe sepsis, and septic shock.

Objective:To compare the course of arginine vasopressin (AVP) and copeptin plasma concentrations between patients with infection, severe sepsis, and septic shock. Design:Prospective, closed-cohort study. Setting:Twelve-bed general and surgical intensive care unit and 33-bed internal medicine ward in a university hospital. Patients:Ten patients with infection, 22 with severe sepsis, and 28 with septic shock. Interventions:None. Measurements and Main Results:Hemodynamic, laboratory and clinical data were recorded daily during the first 7 days after intensive care unit or hospital admission. Parallel thereto, blood was withdrawn to determine plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations. Standard tests, a mixed effects model, and a linear regression analysis were used for statistical analysis. The AVP response was different between the three study groups (p < 0.001) but did not change over time (p = 0.12). Although patients with severe sepsis and septic shock had higher AVP levels than did patients with infection (both p < 0.001), no difference in AVP concentrations was seen between severe sepsis and septic shock patients (p = 0.98). No difference in AVP was observed between survivors and nonsurvivors at day 28 (p = 0.87). In patients with severe sepsis, serum osmolarity (p < 0.001), arterial pH (p = 0.001), lactate (p < 0.001), and Pao2 (p = 0.04) were associated with the course of AVP plasma levels, whereas it was serum osmolarity alone in patients with septic shock (p = 0.03). Plasma AVP concentrations correlated with copeptin (r = .614, p < 0.001), but this correlation was influenced by continuous veno-venous hemofiltration (p = 0.002). Conclusions:Severe sepsis induced a stronger AVP response than infection without systemic inflammation. However, the lack of a difference in AVP plasma concentrations between patients with and without shock indicates that the AVP system does not function normally in severe sepsis. Our data support the hypothesis that impaired AVP response is at least partially responsible for the failure to restore vascular tone in septic shock.

Anesthesia and Its Allied Disciplines in the Developing World: A Nationwide Survey of the Republic of Zambia

BACKGROUND: Many surgical interventions worldwide are performed in developing countries. To improve survival of acutely and critically ill patients in these countries, basic problems and demands of anesthesia care need to be identified. Using this survey, we evaluated the current status of anesthesia and its allied disciplines (intensive care medicine, emergency medicine, and pain therapy) in the Republic of Zambia. METHODS: Questionnaires were sent to 87 hospitals registered at the Zambian Ministry of Health as performing minor or major surgery. The questionnaire consisted of 111 questions grouped into five sections: general hospital information, anesthesia, intensive care, emergency medicine, and pain therapy. RESULTS: Sixty-eight questionnaires could be statistically evaluated (78%). The most common operations were obstetric/gynecological and abdominal surgical procedures. Dissociative ketamine anesthesia was the technique most often used for general anesthesia (50%). Endotracheal intubation was performed in 10% of patients undergoing general anesthesia. In most hospitals (78%), anesthesia was administered by nonphysicians. Only 5 of 68 hospitals (7%) reported having an intensive care unit, with 29 beds to serve the entire country. Anesthesiologists play almost no role in emergency medicine and pain therapy. CONCLUSIONS: Anesthesia in the Republic of Zambia is a highly under-developed and under-resourced medical specialty.

Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression

IntroductionThe multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function.MethodsThis retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 ± 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis.ResultsHeart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 ± 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P < 0.001). Cardiac index and cardiac power index remained unchanged whereas stroke volume index increased (P = 0.002). In two patients (5%), metoprolol was discontinued because of asymptomatic bradycardia. Norepinephrine and milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%.ConclusionLow doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy and their influence on proinflammatory cytokines are warranted.

Histologic pathologies of the myocardium in septic shock: a prospective observational study.

ABSTRACT Myocardial depression in septic shock is well known, but its pathophysiological genesis is incompletely understood. To assess the incidence and extent of stress-induced histologic myocardial alterations in septic shock, a prospective, observational, combined clinical and postmortem study was conducted, and 20 patients dying from septic shock were included. Exclusion criteria were younger than 18 years, pregnancy, open heart surgery or cardiopulmonary resuscitation, acute neurologic diseases, pheochromocytoma, and forensic autopsy. A systematic macropathologic evaluation was performed. Nine predefined heart sections were histologically screened for myocytolysis, interstitial fibrosis, contraction band necrosis, mononuclear infiltrates, interstitial edema, and tissue hemorrhage. Stress-induced pathologies were found in 90% to 100% of patients in all heart sections (myocytolysis, 100%; interstitial fibrosis, 100%; contraction band necrosis, 95%; mononuclear infiltrates, 90%; interstitial edema, 90%; tissue hemorrhage, 30%). The incidence and extent of contraction band necrosis, mononuclear infiltrates, and myocytolysis did not differ between sexes; patients with or without chronic &bgr;-blocker, calcium antagonist, and/or statin premedication; or between the binary use of different catecholamine agents (all comparisons P > 0.05). The maximum epinephrine dose correlated with the overall extent of mononuclear infiltrates (Spearman-Rho, r = 0.704; P = 0.05) and myocytolysis (Spearman-Rho, r = 0.933; P = 0.001). Maximum norepinephrine doses correlated with the extent of mononuclear infiltrates in the left ventricular anterior wall (Spearman-Rho, r = 0.519; P = 0.02). The total duration of catecholamine therapy was correlated with the extent of mononuclear infiltrates in the apex (Spearman-Rho, r = 0.571; P = 0.009) and right atrium (Spearman-Rho, r = 0.535; P = 0.02). In conclusion, our results suggest that histologic lesions potentially indicative of stress-induced cardiotoxicity can be observed in most patients dying from septic shock.

Endogenous vasopressin and copeptin response in multiple trauma patients

Endogenous arginine vasopressin (AVP) levels in multiple trauma patients are unknown. Arginine vasopressin is considered to play an important role in severe hemorrhage. In this prospective study, 87 multiple trauma patients (Injury Severity Score >15) and 50 healthy volunteers were enrolled. On admission to the emergency department (ED), demographic, clinical, and laboratory data were documented, and blood was sampled for determination of AVP (radioimmunosassay) and copeptin, a stable fragment of the AVP precursor (immunoluminometric assay). In patients requiring intensive care unit (ICU) therapy, blood and data sampling were repeated at 4, 6, and 24 h after ED admission. Linear logistic and mixed-effects regression analyses were used for statistical analysis. On ED admission, AVP plasma concentrations (43.2 ± 84.9 pM) were significantly increased when compared with controls (0.92 ± 0.44 pM, P < 0.001). Plethysmographic oxygen saturation was the only parameter independently associated with AVP (regression coefficient, −0.126; 95% confidence interval, −0.237 to −0.014; P = 0.03). No correlation was observed between AVP and survival (P = 0.62), hemodynamic variables (systolic arterial pressure, P = 0.24; MAP, P = 0.59; diastolic arterial pressure, P = 0.74; central venous pressure, P = 0.36), or brain trauma (P = 0.46). In ICU patients, AVP decreased during the first 24 h (P < 0.001) and was independently associated with heart rate (P = 0.02) and blood glucose (P = 0.009). Copeptin concentrations were correlated with AVP (r2 = 0.718, P < 0.001). In conclusion, AVP was significantly increased in multiple trauma patients and seems to be an integral part of the neuroendocrine response to severe injury. In ICU patients, AVP decreased to moderately elevated levels within 24 h after ED admission.

Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study

IntroductionDeep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients.MethodsAFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin.ResultsFour hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels <0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels.ConclusionStandard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.