L. S. Weilemann

B-Type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients

Introduction:In early stages of septic shock, impaired myocardial function plays an important prognostic role. In this context, B-type natriuretic peptide (BNP) has been shown to be a neurohumoral marker for left ventricular dysfunction, because myocardial strain and ischemia both increase BNP concentration. The present study was designed to test if BNP allows for identification of patients at risk for developing sepsis-induced myocardial depression and if an increased concentration of BNP is associated with an adverse outcome in patients with septic shock. Methods and Results:In a prospective study, 93 patients with septic shock were divided into one group with normal ventricular function (left ventricular ejection fraction >50%) on days 3 to 5 (n = 38) and another group of patients with impaired left ventricular function (left ventricular ejection fraction <50%) on days 3 to 5 (n = 55). Patients with impaired left ventricular function had an increased median plasma BNP concentration on day 5 (699 [608 of 795.5] pg/nL vs. 86 [71.3 of 93] pg/nL) and an ejection fraction of 38 ± 6% on day 5 vs. 58 ± 7% in patients without impaired left ventricular function. There was a close inverse relation between increased plasma BNP concentrations and depressed left ventricular ejection fraction (p < 0.05). BNP measured at days 3 and 5 revealed an association with the end point of survival. In the proportional hazards regression model adjusted for age, male gender, and creatinine concentration, measured at days 0, 3, 5, and 12, BNP concentration at day 5 showed an increased hazard for reaching the end point (hazard ratio: 1.407; 95% confidence interval: 1.033–1.916; p = 0.030). In an additional receiver operating characteristic curve analysis, the predictive value of a model including cardiovascular risk factors and additional BNP concentration on day 5, compared with a baseline model of cardiovascular risk factors, improved the area under the curve the most; therefore, this model was suited best for prediction of sepsis-induced myocardial depression and 30-day survival for patients with septic shock. Area under the curve of this model combined with BNP concentration at day 5 for death after 30 days (0.65) impaired left ventricular ejection fraction (0.94) and sepsis-induced myocardial depression (0.96). Conclusion:These results indicate that plasma BNP concentration represents a reliable marker for identification of patients developing sepsis-induced myocardial depression. In addition, BNP concentration on day 5 may be used as a prognostic marker to identify patients with an elevated risk for an adverse outcome.

Antidiabetic medications in overdose : a comparison of the inquiries made to a regional poisons unit regarding sulfonylureas, biguanides and insulin

OBJECTIVE The drugs most commonly used to treat diabetes mellitus are sulfonylureas, biguanides and insulin. The most serious effects seen in overdose with these agents are hypoglycemia or lactic acidosis which may be fatal or cause cerebral defects. The present investigation analyzes inquiries made to a regional poisons unit involving overdoses with sulfonylureas, biguanides and insulin. PATIENTS AND METHODS A total of 218,070 made inquiries between 1995 and 2004 were evaluated. The inquiries were received by telephone and a standardized questionnaire was sent subsequently to the physicians calling for follow-up information. The cases were analyzed with regard to gender, age, etiology, symptoms and clinical outcome. RESULTS 263 inquiries concerning sulfonylureas (48.3% female, 49.4% male, 2.3% sex unknown, average age 39.1 +/- 26.8 years), 172 concerning biguanides (60.5% female, 37.2% male, 2.3% sex unknown, average age 41.5 +/- 24.1 years), and 191 concerning insulin (53.9% female, 41.9% male, 4.2% sex unknown, average age 44.6 +/- 16.7) were made. In cases involving sulfonylureas, the etiology was deliberate self-poisoning in 62.7% and accidental in 31.9% (biguanides 60.5% and 29.1%, insulin 85.3% and 9.4%). Using the Poisoning Severity Score, no symptoms were observed in 41.4% of the patients with sulfonylurea overdose (biguanides 40.1%, insulin 22.5%), minor symptoms in 37.6% (biguanides 32.6%, insulin 33.5%), major symptoms in 14.4% (biguanides 13.4%, insulin 26.2%) and serious symptoms in 4.6% (biguanides 12.2%, insulin 14.7%). Returned questionnaires reporting clinical outcomes showed that a full recovery occurred in most patients (sulfonylureas 97.4%, biguanides 93.0%, insulin 94.4%), cerebral defects persisted in 1.8% of the cases involving sulfonylureas (biguanides 1.5%, insulin 2.4%), and that 0.9% of the patients with sulfonylurea overdose died (biguanides 6.1%, insulin 3.6%). CONCLUSIONS Sulfonylureas were the most frequently observed medication in cases of overdose with antidiabetic agents. Insulin overdose caused the highest number of major and serious symptoms. Overdose with biguanides led to the most deaths.

Epidemiology of hydrogen phosphide exposures in humans reported to the poison center in Mainz, Germany, 1983-2003.

Background. Poisonings with rodenticides containing hydrogen phosphide-releasing compounds may lead to deleterious organ dysfunction and death. Since data of hydrogen phosphide poisonings is limited to case reports/series, this study was intended to elucidate hydrogen phosphide poisonings based on a 20-year data collection. Methods. Explorative data analysis of the Poison Center Mainz database looking for route of exposure, symptoms, and severity using the Poisoning Severity Score. Results. From 1983–2003, 188 hydrogen phosphide poisonings were reported. Sixty-five percent of these were unintentional residential, 28% attempts to commit suicide (intentional), 5% occupational, and 2% undetermined. In the majority of intentional poisonings the poison was ingested, whereas in unintentional poisoning of adults inhalation exposure dominated, caused by inappropriate self-protection from the released hydrogen phosphide gas during usage. Frequently observed symptoms in unintentional poisonings were nausea, vomiting, pain, coughing, and dizziness with no further worsening of symptoms. In intentional poisonings frequent symptoms were vomiting, somnolence, seizures, coma, and shock with two initially fatal poisonings. Follow-up on these cases showed a significant worsening of symptoms and a two-fold increase in fatal poisonings. Conclusion. Route of exposure, severity of symptoms, and the necessary treatment differs substantially between unintentional and intentional poisonings. In this study, two initially symptomatic intentional poisonings were later reported fatal. Careful monitoring is recommended in symptomatic intentional poisonings.

Subacute coronary stent thrombosis in a patient developing clopidogrel associated thrombotic thrombocytopenic purpura

Clopidogrel, in combination with aspirin, is commonly used for the prevention of thrombosis in patients who have received coronary artery stents. As a rare but critical complication, clopidogrel associated thrombotic thrombocytopenic purpura (TTP) has previously been described. A 78 year old man presented with unstable angina and filiform subtotal stenosis of the left anterior descending artery. He was treated with balloon angioplasty and stent implantation. After four days the patient again had angina caused by stent thrombosis, which was treated with balloon angioplasty. During hospital stay the typical course of clopidogrel associated TTP was observed with thrombocytopenia and petechial purpura occurring 14 days after drug initiation and prompt response to therapeutic plasma exchanges. These findings strongly suggest that clopidogrel may have increased platelet activation and aggregation in this immunologically susceptible patient, ultimately leading to a stent thrombosis.

Shunting of the Microcirculation After Mesenteric Ischemia and Reperfusion Is a Function of Ischemia Time and Increases Mortality

Objective: Shunting of the microcirculation contributes to the pathology of sepsis and septic shock. The authors address the hypothesis that shunting of the microcirculation occurs after superior mesenteric artery occlusion (SMAO) and reperfusion, and explore functional consequences.

Anti-Inflammatory Treatment with Standardized Human Serum Protein Solution Reduces Local and Systemic Inflammatory Response after Hemorrhagic Shock

Objective: Reperfusion after hemorrhagic shock leads to local and systemic inflammatory response. This study evaluates the effect of a short-term treatment with standardized human serum protein solution (SPS) on the local and systemic inflammatory response in the mesenteric microcirculation in the rat. Methods: Spontaneously breathing animals underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume-controlled hemorrhagic shock was set by arterial blood withdrawal (2.5 ml/100 g body weight for 60 min), followed by reperfusion for 4 h. SPS (n = 10) or saline 0.9% (controls, n = 10) was given intravenously as a continuous infusion for 30 min at the beginning of reperfusion (‘pre-hospital’). This was followed in both groups by substitution of blood and normal saline to support blood pressure (‘in-hospital’). Systemic hemodynamics, mesenteric microcirculation and arterial blood gases were monitored before, during and after shock, and for 4 h after initiation of reperfusion. Results: SPS treatment markedly reduced leukocyte/endothelial interaction, and reduced the need for intravenous fluids compared to controls. For the entire observation period, blood pH was unchanged from baseline only in SPS-treated animals. The improvement of base excess and abdominal blood flow persisted for 2 h after SPS infusion. Conclusion: Short-term SPS treatment of hemorrhagic shock improved mesenteric microcirculation, arterial blood gases and global hemodynamics, and attenuated the inflammatory response to reperfusion. It may provide clinical benefit when applied at an early phase of reperfusion after hemorrhagic shock.

Significance of hyperlactatemia in acute hypnotic drug poisoning

SummaryLactate concentration, fibrinogen and fibrin(ogen) — degredation-products in central venous blood were analysed in 35 unconscious patients with acute hypnotic drug poisoning (HDP) and compared with the results in 13 healthy control persons undergoing the same degree of forced diuresis via central venous catheters. Blood samples were taken on admission and at 12 h intervals up to 36 h after admission. Patients with HDP were attributed to the categories of moderate intoxications (n=17) and severe intoxications (n=18) according to their clinical condition. On admission, blood lactate was significantly higher in severe intoxication (3.90±2.94 mmol/l) as compared to the control group (1.25±0.17 mmol/l). Blood lactate was less elevated in moderate poisoning (2.74±1.22 mmol/l). Thirty-six hours after admission blood lactate was completely normalised in patients with moderate intoxication (1.19±0.69 mmol/l) but still significantly elevated in severely poisoned patients (2.26±1.48 mmol/l). Lactate concentration was above normal in 15 out of 17 patients with moderate and in 17 out of 18 patients with severe poisoning. A statistically significant linear correlation existed between the duration of unconsciousness and the maximal lactate concentration within 12 hrs after admission. For fibrinogen concentrations statistically significant differences were observed neither between groups nor across time. Titers of FDP were elevated in 9 out of 11 patients with moderate and to a higher degree in all patients with severe poisoning, indicating low rate DIC.Hyperlactatemia is a frequent finding in acute hypnotic drug poisoning. Blood lactate estimations may improve the evaluation of the severity of poisoning and the efficacy of therapeutic interventions.ZusammenfassungBei 35 Patienten mit Bewußlosigkeit infolge akuter exogener Intoxikationen durch Arzneimittel wurden die Konzentrationen von Lactat und Fibrinogen sowie die Fibrin(ogen)-Spaltprodukttiter im zentralvenösen Blut gemessen und mit den Ergebnissen bei 13 gesunden Kontrollpersonen, die in gleicher Weise einer forcierten Diurese über zentrale Venenkatheter unterzogen wurden, verglichen. Blutproben wurden nach der Aufnahme und dann in 12stündlichen Abständen bis 36 h nach Klinikaufnahme entnommen. Die intoxikierten Patienten wurden nach dem klinischen Aufnahmebefund in mittelschwere Vergiftungen (n=17) und schwere Vergiftungen (n=18) gegliedert. Bei der Aufnahme war der mittlere Blutlactatspiegel bei den Patienten mit schweren Vergiftungen (3,90±2,94 mmol/l) signifikant höher als in der Kontrollgruppe (1,25±0,17 mmol/l). Der Blutlactatspiegel war bei den Patienten mit mittelgradiger Vergiftung geringgradig erhöht (2,74±1,22 mmol/l) und lag ebenfalls signifikant über den Kontrollwerten. 36 Stunden nach Aufnahme waren die Lactatspiegel bei Patienten mit mittelschweren Vergiftungen völlig normalisiert (1,19±0,69 mmol/l), bei den Patienten mit schweren Vergiftungen jedoch noch signifikant erhöht (2,26±1,48 mmol/l). Im einzelnen fand sich eine Hyperlactatämie bei 15 von 17 Patienten mit mittelgradigen und bei 17 von 18 Patienten mit schweren Vergiftungen. Es bestand eine statistisch signifikante lineare Korrelation zwischen der Dauer der Bewußlosigkeit und den maximalen Lactatkonzentrationen innerhalb 12 Stunden nach Aufnahme. Die mittleren Fibrinogenspiegel zeigten keine signifkanten Unterschiede im Zeitverlauf oder zwischen den Gruppen. Die Titer der Fibrinogen-Spaltprodukte waren bei 9 von 11 Patienten mit mittelschweren Vergiftungen mäßig und bei allen Patienten mit schweren Vergiftungen deutlich gesteigert, was den Hinweis auf eine ablaufende Verbrauchskoagulopathie gibt. Durch Bestimmung des Blutlactates im Verlauf können die Schweregradeinteilung von Patienten mit Vergiftungen verbessert und die Wirksamkeit verschiedener Therapieverfahren auf die Dauer der Bewußtlosigkeit objektiv verglichen werden.