[Not all drugs are the same]. / Droge ist nicht gleich Droge.

Drug use has changed dramatically in recent years. Classic drugs such as marijuana, heroin, and cocaine are being pushed progressively into the background. Consumer behavior has also changed and so-called designer drugs dominate the market. Designer drugs are synthetic or semi-synthetic drugs based on a well-known substance. Mostly amphetamine derivates, synthetic cannabinoids, and synthetic cathinone are used. Legal monitoring capabilities are limited, since these substances are so-called legal highs and are commercially available. A ban often follows a latency period. Estimating the risk is difficult, and the problem of intoxication increases. This overview presents the activity profiles and risks of classic and new drugs.

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. METHODS: Spontaneously breathing animals (rats) (n = 30) underwent SMAO for 0 (controls), 30 (SMAO_30) or 60 min (SMAO_60) followed by reperfusion (4 h) with normal saline. Leukocyte-endothelial interactions in mesenteric venules were quantified in an exteriorized ileal loop using intravital microscopy. Abdominal blood flow was recorded continuously, and arterial blood gases were analyzed at intervals. The above groups were matched by comparable groups with continuous superior mesenteric artery blood flow measurements and without exteriorizing an ileal loop (controls*, SMAO_30*, SMAO_60*). RESULTS: Adherent leukocytes increased shortly after reperfusion in ischemia groups, and plateaued in these groups. Centerline velocity in the recorded venules was significantly reduced after reperfusion down to low-flow/no-flow in SMAO_60 as compared to SMAO_30 and controls, whereas perfusion of the SMA and ileal vessels persisted. The microcirculatory changes in SMAO_60 were accompanied by progressive metabolic acidosis, substantially larger volumes of intravenous fluids needed to support arterial blood pressure and significantly reduced survival (30%). SMA blood flow increased in relation to abdominal blood flow after reperfusion in SMAO_60*, and remained constant in SMAO_30* and controls*. Survival was 80% in SMAO_60*. CONCLUSION: Shunting of the microcirculation can be observed after SMAO for 60 min and reperfusion, and contributes significantly to the pathology of mesenteric ischemia and poor outcome.

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.

Antidiabetic medications in overdose: a comparison of the inquiries made to a regional poisons unit regarding original 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.

[Drug poisonings in childhood at a regional poisons unit]. / Intoxikationen mit Medikamenten im Kindesalter bei einem regionalen Giftinformationszentrum.

BACKGROUND: Drug poisonings in childhood account with about one fourth for the most important group of poisonings in this age group. METHOD: From 1995 to 2004 the inquiries to a poison centre regarding drug poisonings of children < or = 6 years of age were analyzed. Additionally, a standardized questionnaire was sent for follow-up information. RESULTS: During the study period a total number of 17 553 cases of drug poisonings in childhood was determined and follow-up information was obtained for 8 590 cases (48.9 %). Boys were more likely to be affected (53.4 %) and most children were between 2 and 4 years of age (57.5 %). Mostly oral contraceptives, homeopathic drugs, nonsteroidal anti-inflammatory drugs, sodium fluoride and paracetamol were ingested. In 97.8 % of the reported cases none or minor symptoms and in 1.5 % medium or major symptoms (1 death) were observed. In the latter group of patients mostly neuroleptics, antihistaminics, nonsteroidal anti-inflammatory drugs, beta2-sympathomimetics and paracetamol were ingested. In most cases the application of fluids (47.3 %) or activated charcoal (32.0 %) was sufficient. CONCLUSIONS: Severe symptoms have rarely been observed in drug poisonings and in most children a treatment by non-professionals was sufficient. Most frequently activated charcoal was currently used for primary poison elimination. We suggest an early involvement of a poison centre in drug intoxications.

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.

[Systemic fibrinolytic therapy using urokinase in central retinal artery occlusion. A case study]. / Systemische fibrinolytische Therapie mit Urokinase bei Zentralarterienverschluss der Netzhaut. Eine Fallstudie.

BACKGROUND AND OBJECTIVE: Systemic fibrinolysis has become an important therapeutical option in patients with thrombotic occlusion of coronary or pulmonary arteries. In view of the hemorrhagic risk systemic fibrinolytic therapy for retinal vessel occlusion has been discussed controversial. In the present case study results and complications of systemic fibrinolysis should be investigated in patients with central retinal artery occlusion. PATIENTS AND METHODS: From 1995 to 2002 a case series of 19 consecutive patients (8 female, 11 male, age: 63.2+/-14,3 years) with central retinal artery occlusion were treated by systemic application of urokinase using a standardized scheme. The latency from initial symptoms until the initiation of therapy and the medical history of the patients were documented. Visual acuity was determined on admission and before discharge and possible complications were documented. Additionally, screening investigations for genetic thrombophilia were performed. RESULTS: 15 patients showed an improvement of the visual acuity (79 %, 95 %-KI: 54 %-94 %). For 3 patients no improvement and for one patient a decrease of the visual acuity was determined. Hemorrhagic complications were observed in two patients (11 %, 95 %-KI: 1 %-33 %). As these minor bleedings were self-limiting the fibrinolytic therapy was discontinued only in one patient. As risk factors most commonly arterial hypertension (68 %) and smoking (26 %) were identified. In 4 patients a genetic thrombophilia was diagnosed. CONCLUSIONS: Considering the poor prognosis of central retinal artery occlusion and the disappointing results of conservative treatment, an improvement of the visual acuity in the absence of critical complications was observed with systemic fibrinolytic therapy in the presented case study. However, only controlled trials can provide proof for the effect of fibrinolysis versus spontaneous improvement.

Experiences of a poison center network with renal insufficiency in acetaminophen overdose: an analysis of 17 cases.

OBJECTIVE: Renal insufficiency is less common than liver failure in acetaminophen overdose but renal tubular damage occurs even in the absence of hepatotoxicity. Data published on this topic are rare consisting mostly of case reports or reports in a small number of patients. Presently, a larger number of patients with renal insufficiency associated with acetaminophen overdose should be analyzed using a multicenter approach. STUDY DESIGN: Retrospective analysis of patients with acetaminophen-related nephrotoxicity reported to a poison center network from 1995 to 2003. Renal insufficiency was defined as elevated serum creatinine of more than double of the normal range (>2.4 mg/dL [212 micromol/L]). Patients were classified into 4 groups (A: creatinine 2.4-5.0 mg/dL, B: creatinine>5.0 mg/dL requiring no dialysis, C: creatinine>5.0 mg/dL requiring dialysis, D: creatinine>5.0 mg/dL with fatal outcome). RESULTS: Seventeen patients were included (8 female, 9 male, average age 31.7 +/- 21.1 yrs) with 6 patients in group A (B: 7, C: 2, D: 2). In 5 patients renal insufficiency occurred without elevation of liver enzymes. Regarding possible risk factors 5 patients concomitantly ingested nephrotoxic substances, 4 presented with dehydration due to vomiting, 4 with chronic excessive dosing (overdose) of acetaminophen, 3 showed pre-existing renal insufficiency, 2 pre-existing liver disease and 2 died with multiple organ failure. CONCLUSIONS: Renal insufficiency in acetaminophen overdose mostly resolved without dialysis and occurred isolated without hepatotoxicity in less than one-third of the investigated patients. Conditions which might play a role as influencing factors for renal complications included concomitant ingestion of nephrotoxic drugs, dehydration, chronic excessive dosing (overdose) of acetaminophen, pre-existing renal or liver disease and multiple organ failure. Renal function should be monitored in acetaminophen overdose particularly in patients showing the latter comorbidity.

Prolonged recirculation is required to detect secondary metabolic and hemodynamic deterioration after superior mesenteric artery occlusion.

We evaluated late (4 hrs) effects of reperfusion on hemodynamics after 30 or 60 min occlusion of the superior mesenteric artery (SMA) in a rat model. Spontaneously breathing animals (n=30) underwent occlusion of the SMA for 0 (sham), 30 (SMAO_30) or 60 min (SMAO_60) followed by reperfusion with normal saline. Abdominal blood flow (ABF), SMA blood flow (SBF), arterial blood pressure and heart rate were recorded continuously. Systemic vascular resistance (SVR) and SMA vascular resistance (MVR) were calculated at baseline and after 240 min reperfusion (240R). All animals survived in SMAO_30 and sham, two died in SMAO_60 after 120R. ABF remained constant in all groups. SVR increased in SMAO_30 and sham and decreased in SMAO_60 at 240R. SBF was significantly lower after reperfusion in ischemia groups as compared to sham. After 120R, SBF had increased significantly in SMAO_60 versus SMAO_30. MVR increased significantly in SMAO_30 but not in SMAO_60 and sham at 240R. 60 minutes SMA occlusion revealed early hemodynamic changes of septic circulation with increased blood flow in the SMA, decreased SVR, and pseudo-normalization of MVR. Prolonged observation periods are required to detect these significant changes which are overlooked when only studying 120 minutes of reperfusion as usually done.

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.

Epidemiological assessment of 160 cases of insulin overdose recorded in a regional poisons unit.

OBJECTIVE: Overdoses with insulin are common, and cases of hypoglycemic coma can be fatal and cause cerebral defects. However, data published on this topic are rare, consisting mostly of case reports or reports in a small number of patients. The present investigation analyzes inquiries made to a regional poisons unit involving overdoses with insulin. PATIENTS AND METHODS: A total of 175,890 inquiries for the years 1995-2003 (until September) were evaluated. 160 inquiries were received by telephone concerning insulin overdoses, and a standardized questionnaire was sent to the physicians asking for follow-up information. The cases were analyzed in regard to etiology, type of insulin used, concomitant substances being taken by the patient, symptoms and clinical outcome. RESULTS: Of the 160 inquiries investigated, 53.1% of the patients were female, 43.1% male and in 3.8% the sex of the patient was unknown. The average age was 44.7 years. 89.4% involved suicidal or parasuicidal cases, 5.0% were accidental overdoses and 1.9% involved cases of criminal overdose (3.7% were for other reasons). Rapidly acting insulins (57.8%) were used more commonly than long-acting formulations (42.8%). Benzodiazepines were the most frequently ingested concomitant medication (37.5%) with ethanol 15.6%, antihypertensive drugs 12.5% and antidepressants 10.0%. Most patients presented with a delay of 2-3 hours after insulin administration (15.0%). Almost 50% of the patients presented within the first 6 hours. According to the Poisoning Severity Score, no symptoms were observed in 16.8% of the patients, minor symptoms in 36.8%, major symptoms in 25.2% and serious symptoms in 21.3%. Information concerning the clinical outcome (75 cases) showed that a full recovery occurred in most patients (94.7%), but in 2.7% there were cerebral defects and 2.7% of the patients died. CONCLUSIONS: The etiology of overdoses with insulin was mainly deliberate self-poisoning. Physicians should take into account that long-acting insulin formulations and concomitant substances were frequently used. For overdoses with insulin, relatively high rates of serious symptoms and deaths were observed.

Experiences of a poison center with metformin-associated lactic acidosis.

Metformin is widely used in the treatment of type 2 diabetes, though it is recognized to be associated with the risk of lactic acidosis. A case of pronounced lactic acidosis with cardiac arrest (pH 6.60, lactate 17.5 mmol/l, base excess - 30, standard bicarbonate 2.5 mmol/l, core body temperature 27.8 degrees C) is presented in a 61-year-old woman under metformin therapy. The key laboratory abnormalities observed during the intensive care treatment including repeated hemodialysis are described. The patient showed a complete recovery with residually reduced mental capabilities. Furthermore, an explorative data analysis of our poison center database from 1995 until 2003 concerning metformin was performed. In 109 inquiries for metformin a lactic acidosis (mean pH 6.87 +/- 0.11, mean lactate 20.9 +/- 8.1 mmol/l) was present in 14 cases (9 female, 5 male, average age 57.7 years) with 8 patients under regular metformin therapy and 6 patients who ingested large amounts of metformin to attempt suicide. 4 patients did not survive the severe metabolic disturbance. The present report demonstrates that metformin-associated lactic acidosis is a rare but critical complication of metformin therapy of type 2 diabetes as well as in acute suicidal ingestion of metformin. Early diagnosis and rapid correction of the metabolic acidosis using hemodialysis provides the possibility of a positive outcome even in severe cases. If metformin-associated lactic acidosis is suspected we recommend early involvement of a poison center.

Epidemiology of cardiac dysrhythmias in acute intoxication.

Cardiac dysrhythmias are common in acute intoxications. However, epidemiological data is rare and restricted to specific substances. From 1995 to 2003 (until September) 91 285 inquiries of physicians and paramedics to a poison center regarding acute intoxications were analyzed revealing 9888 patients (10.8%) suffering from disturbances of the cardiac rhythm. In a first step of the explorative data analysis dysrhythmias were graduated into three categories (I: tachycardia/bradycardia; II: arrhythmia/conduction disorder; III: ventricular dysrhythmia/cardiac arrest) and the frequencies of the involved substances were determined. In a second step substances which resulted to be of significant interest were investigated for their specific pattern of dysrhythmias. For category I (n = 8730) predominantly tricyclic antidepressants, neuroleptics, benzodiazepines, betablockers, and nonsteroidal antiinflammatory drugs were registered (II: [n = 949] tricyclic antidepressants, digitalis glycosides, benzodiazepines, neuroleptics, Ca antagonists; III: [n = 209] tricyclic antidepressants, neuroleptics, sotalol, ethanol, central nervous system stimulants). Tricyclic antidepressants resulted in 23.4% of the reported cases in symptoms of category I (II: 2.3%, III: 0.6%; n = 8535). The highest rates of dysrhythmias were observed for sotalol (I: 34.7%, II: 21.6%, III: 8.0%; n = 176) as compared to the lowest rates found for paracetamol (I: 5.2%, II: 0.3%, III: 0.1%; n = 6429). The present investigation provided a comprehensive clinical overview about the frequency of dysrhythmias and involved substances during acute poisonings in emergency medicine. Furthermore, the specific effects of selected substances concerning dysrhythmias could be determined in view of a clinical database.

Size of pancreatic islets of Langerhans: a key parameter for viability after cryopreservation.

Large amounts and excellent viabilities of pancreatic islets are prerequisites for recent advances in islet transplantation. Cryopreservation has been shown to enlarge transplanted cell mass, but has been accompanied by reduced viability. In this study rat pancreatic islets were differentiated into small (<200 micro m), medium (200-400 micrometers) and large (>400 micrometers) categories and their susceptibilities to different freezing conditions were evaluated: concentration of cryoprotectant (0.7-3.1 M), equilibration (15 vs. 45 min, 22 degrees C vs. on ice) and post-thaw removal of cryoprotectant (15 vs. 30 min, stepwise vs. one-step). The most prominent finding was a negative correlation between islet size and viability observed in non-frozen islets to a minor degree (r=-0.44) and significantly enhanced after cryopreservation (r<-0.8). The concentration of cryoprotectant showed the most significant influence on viability affecting small, medium and large islets. Different techniques of equilibration with the cryoprotectant resulted in significant changes of islet viability of medium islets, whereas small and large islets were unaffected. For different techniques of removal of the cryoprotectant, no significant influence on viabilities was found. We conclude that large islets represented a highly susceptible population concerning damage due to cryopreservation.

[Fulminant pulmonary edema in falciparum malaria [corrected]]. / Fulminantes Lungenödembei Malaria tropica.

HISTORY AND ADMISSION FINDINGS: A 54-year-old man was admitted because of intermittent fever for 2 days. Ten days earlier he had returned from Kenya. He had not taken any antimalarial drugs prophylactically. INVESTIGATIONS: Initial blood smears showed Plasmodium falciparum in 10.4% of erythrocytes. Laboratory tests indicated hyponatremia and disseminated intravascular coagulation. Also, laboratory markers of infection and hemolysis were clearly positive and accompanied by a low-grade normocyticanaemia. Chest radiograph showed the heart size to be at the upper limit of normal and no signs of congestion, pleural effusion or inflammatory infiltrates. Sonography demonstrated hepatosplenomegaly with diffusely increased echogenicity of the liver. TREATMENT AND COURSE: Falciparum malaria [corrected] with quartan fever was diagnosed and treatment with quinine and doxycycline was initiated. Despite the successful elimination of parasites and a negative fluid balance the patient died two days after admission from pulmonary edema and heart failure. CONCLUSIONS: A negative fluid balance failed to prevent acute pulmonary edema in this case of severe malaria,supporting the view that fluid imbalance is not an essential feature in malaria-induced lung injury and that cytokines play and important role.