Susanne Blum

Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial.

OBJECTIVES To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay. DESIGN A prospective, randomized, blinded, controlled clinical trial. SETTING A university hospital ICU. PATIENTS Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment. INTERVENTIONS Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale). MEASUREMENTS AND MAIN RESULTS The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group. CONCLUSIONS There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.

Intercurrent complications in chronic alcoholic men admitted to the intensive care unit following trauma

ObjectiveA chronic alcoholic group following trauma was investigated to determine whether their ICU stay was longer than that of a non-alcoholic group and whether their intercurrent complication rate was increasedDesignProspective study.SettingAn intensive care unit.PatientsA total of 102 polytraumatized patients were transferred to the ICU after admission to the emergency room and after surgical treatment. Of these patients 69 were chronic alcoholics and 33 were allocated to the non-alcoholic group. The chronic-alcoholic group met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in these patients was ≥60 g. Diagnostic indicators included an alcoholismrelated questionnaire (CAGE), conventional laboratory markers and carbohydrate-deficient transferrin.Measurement and resultsMajor intercurrent complications such as alcohol withdrawal syndrome (AWS), pneumonia, cardiac complications and bleeding disorders were documented and defined according to internationally accepted criteria. Patients did not differ significantly between groups regarding age, TRISS and APACHE score on admission. The rate of major intercurrent complications was 196% in the chronic alcoholic vs 70% in the non-alcoholic group (P=0.0001). Because of the increased intercurrent complication rate, the ICU stay was significantly prolonged in the chronic-alcoholic group by a median period of 9 days.ConclusionsChronic alcoholics are reported to have an increased risk of morbidity and mortality. However, to our knowledge, nothing is known about the morbidity and mortality of chronic alcoholics in intensive care units following trauma. Since chronic alcoholics in the ICU develop mor major complications with a significantly prolonged ICU stay following trauma than non-alcoholics, it seems reasonable to intensify research to identify chronic alcoholics and to prevent alcohol-related complications.

Relevance of Carbohydrate-deficient Transferrin as a Predictor of Alcoholism in Intensive Care Patients following Trauma

Every second traumatized patient is a chronic alcoholic. Chronic alcoholics are at risk due to an increased morbidity and mortality. Reliable and precise diagnostic methods for detecting alcoholism are mandatory to prevent posttraumatic complications by adequate prophylaxis. The patients history, however, is often not reliable, and conventional laboratory markers are not sensitive or specific enough. The aim of this study was to investigate whether carbohydrate-deficient transferrin (CDT) is a sensitive and specific marker to detect alcoholism in traumatized patients. One hundred and five male traumatized patients or their relatives gave their written informed consent to participate in this institutionally approved study. All patients were transferred to the intensive care unit after admission to the emergency room, followed by surgical treatment. Diagnostics included an alcoholism-related questionnaire, conventional laboratory markers (mean corpuscular volume, gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase), and CDT sampling (microanion-exchange chromatography, turbidimetry, and radioimmunoassay, respectively). Only patients in whom a reliable history could be obtained were included. Alcoholism was diagnosed if the patients met the Diagnostic and Statistical Manual of Mental Disorders criteria for chronic alcohol abuse or dependence. The administration of fluids before CDT sampling was carefully documented. Patients did not differ significantly regarding age, Trauma and Injury Severity Score, and Acute Physiology and Chronic Health Evaluation score. The sensitivity of the CDT research kit was 70% and of the commercially available kit CDTect was 65%. Early sampling in the emergency room and before administration of large volumes of fluid increased the sensitivity to 83% for the CDT research kit and 74% for CDTect, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

β‐Carbolines in chronic alcoholics following trauma

In our society every second polytraumatized patient is a chronic alcoholic. A patients alcohol‐related history is often unavailable and laboratory markers are not sensitive or specific enough to detect alcohol‐dependent patients who are at risk of developing alcohol withdrawal syndrome (AWS) during their post‐traumatic intensive care unit (ICU) stay. Previously, it has been found that plasma levels of norharman are elevated in chronic alcoholics. We investigated whether β‐carbolines, i.e. harman and norharman levels, could identify chronic alcoholics following trauma and whether possible changes during ICU stay could serve as a predictor of deterioration of clinical status. Sixty polytraumatized patients were transferred to the ICU following admission to the emergency room and subsequent surgery. Chronic alcoholics were included only if they met the DSM‐III‐R and ICD‐10 criteria for alcohol dependence or chronic alcohol abuse/harmful use and their daily ethanol intake was ≥ 60 g. Harman and norharman levels were assayed on admission and on days 2, 4, 7 and 14 in the ICU. Harman and norharman levels were determined by high pressure liquid chromatography. Elevated norharman levels were found in chronic alcoholics (n = 35) on admission to the hospital and remained significantly elevated during their ICU stay. The area under the curves (AUC) showed that norharman was comparable to carbohydrate‐deficient transferrin (CDT) and superior to conventional laboratory markers in detecting chronic alcoholics. Seventeen chronic alcoholics developed AWS; 16 of these patients experienced hallucinations or delirium. Norharman levels were significantly increased on days 2 and 4 in the ICU in patients who developed AWS compared with those who did not. An increase in norharman levels preceded hallucinations or delirium with a median period of approximately 3 days. The findings that elevated norharman levels are found in chronic alcoholics, that the AUC was in the range of CDT on admission and that norharman levels remained elevated during the ICU stay, support the view that norharman is a specific marker for alcoholism in traumatized patients. Since norharman levels increased prior to the onset of hallucinations and delirium it seems reasonable to investigate further the potential role of norharman as a possible substance which triggers AWS.

Reliability of Carbohydrate-Deficient Transferrin to Detect Chronic Alcohol Misuse in Carcinoma Patients

The patients’ history and conventional laboratory markers are often not sensitive or specific enough to detect chronic alcohol misuse, preoperatively. We investigated whether carbohydrate-deficient tr

β-Carbolines in alcohol-dependent intensive care patients during prophylactics and therapy of alcohol withdrawal syndrome

The primary aim of this study was to investigate whether the naturally occurring beta‐carbolines norharman and harman differed between alcohol‐dependent patients who developed alcohol withdrawal syndrome (AWS) and those who did not. The secondary aim was to determine whether different treatment regimens influenced the levels of the beta‐carbolines. Thirty chronic alcoholics with carcinoma of the upper digestive tract were included in this study. They were prophylactically treated by two different medical regimens: flunitrazepam and clonidine (FNZ regimen) and gamma‐hydroxybutyrate and clonidine (GHB regimen). Patients exceeding the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA‐Ar) score of 20 were assigned to the AWS therapy group and received haloperidol in addition to their prevous prophylactic treatment. Patients without AWS remained in the prophylactic group. From days 1–4 of the intensive care unit (ICU) stay norharman, but not harman, was increased in the AWS therapy group. In the FNZ regimen, six of 16 patients (38%) and in the GHB regimen, nine of 14 patients (64%) developed AWS (p= 0.14). Norharman levels did not differ between the two regimens. However, harman levels were increased in the GHB treated regimen on days 1, 2 and 4 following admission to the ICU and correlated with the severity of alcohol withdrawal syndrome. As norharman was elevated in the therapeutically treated ICU patients, this marker appears to be involved in the pathogenesis of AWS. As harman was elevated before and during hallucinations on the GHB regimen, it seems reasonable to carry out further investigations into the potential role of harman as a hallucinatory substance.

Prophylaxis of Alcohol Withdrawal Syndrome in Alcohol-Dependent Patients Admitted to the Intensive Care Unit After Tumour Resection

Prophylaxis of alcohol withdrawal syndrome (AWS) in alcohol-dependent patients shortens the duration of stay in the intensive care unit (ICU). The objective of this study was to assess the effect of four different prophylactic regimens on the duration of ICU stay, prevention of AWS and rate of major intercurrent complications in alcohol-dependent patients admitted to the ICU after tumour resection. A total of 197 alcohol-dependent patients, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (third revised edition) with a daily ethanol intake of 60 g, were allocated randomly to one of the following regimens which were commenced on admission to the ICU: flunitrazepam-clonidine, chlormethiazole-haloperidol, flunitrazepam-haloperidol or ethanol. The duration of ICU stay, prevention of AWS, incidence of tracheobronchitis and major intercurrent complications such as pneumonia, sepsis, cardiac disorders, bleeding disorders and death were documented. On admission, patients did not differ significantly in age, APACHE II and multiple organ failure scores. ICU stay, incidence of AWS, severity of AWS (revised clinical institute withdrawal assessment for alcohol scale > 20) and major intercurrent complication rate did not differ significantly between groups. Although there was no advantage in any of the four regimens with respect to the primary outcome measures, pulmonary and cardiac patients were not included in the study. Patients in the chlormethiazole-haloperidol group had a significantly increased incidence of tracheobronchitis (P = 0.0023), probably because of an increased incidence of hypersecretion.

HTLV-1-associated myelopathy in China : a disease acquired overseas ?

This case report documents the first patient from mainland China with an HTLV-1-associated myelopathy. The available epidemiological data suggest a low rate of HTLV1 infection in China, although the surveys are comparatively small. Possible transmission routes and the risk of encountering the disease outside endemic areas are discussed.This case report documents the first patient from main land China with an HTLV-1-associated myelopathy. The available epidemiological data suggest a low rate of HTLV 1 infection in China, although the surveys are comparatively small. Possible transmission routes and the risk of encountering the disease outside endemic areas are discussed.