Vitamin D levels vary during antiviral treatment but are unable to predict treatment outcome in HCV genotype 1 infected patients.

BACKGROUND: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed. METHODS: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. RESULTS: Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002-1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975-0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000-1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073-2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271-4.695, P = 0.007) constituted the strongest predictors of treatment response. CONCLUSIONS: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.

Fms-like tyrosine kinase 3 receptor ligand (Flt3L)-based vaccination administered with an adenoviral vector prevents tumor growth of colorectal cancer in a BALB/c mouse model.

PURPOSE: Colorectal cancer is the third most frequent cancer in industrial nations. Therapeutic strategies to treat metastatic disease and prevent recurrence are needed. Anti-tumor immunity can be induced by dendritic cells. Dendritic cells can be expanded by the fms-like tyrosine kinase 3 ligand (Flt3L) in vivo. The aim of this study was to develop an adenoviral-based immune-gene therapy of colorectal cancer with Flt3L in a BALB/c mouse model. METHODS: A new Flt3L-encoding adenoviral vector (pAdFlt3L) was administered in two approaches in a CT26 colon cancer model in female BALB/c mice. In the therapeutic approach, pAdFlt3L was injected into the tail vein or directly into subcutaneous CT26 colon carcinoma tumors in BALB/c mice. In the vaccination protocol, mice were vaccinated with CT26 cell lysate and pAdFlt3L subcutaneous prior to subcutaneous application of vital CT26 cells. RESULTS: Application of pAdFlt3L led to high levels of Flt3L in vitro and in vivo. Significant expansion of dendritic cells after application of pAdFlt3L in vivo was confirmed by the use of CD11c and CD11b surface markers in immunohistochemistry and flow cytometry (p = 0.019). In the therapeutic approach, neither intravenous nor intratumoral treatments with pAdFlt3L lead to regression of CT26 tumors. In the vaccination protocol, vaccination completely prevented tumor growth and resulted in superior survival compared to control mice (p < 0.001). CONCLUSIONS: Our results demonstrate that immunostimulatory therapy with pAdFlt3L is effective to prevent tumor development through vaccination and may represent a therapeutic tool to prevent metastatic disease.

Acute cholecystitis: early versus delayed cholecystectomy, a multicenter randomized trial (ACDC study, NCT00447304).

OBJECTIVE: Acute cholecystitis is a common disease, and laparoscopic surgery is the standard of care. BACKGROUND: Optimal timing of surgery for acute cholecystitis remains controversial: either early surgery shortly after hospital admission or delayed elective surgery after a conservative treatment with antibiotics. METHODS: The ACDC ("Acute Cholecystitis-early laparoscopic surgery versus antibiotic therapy and Delayed elective Cholecystectomy") study is a randomized, prospective, open-label, parallel group trial. Patients were randomly assigned to receive immediate surgery within 24 hours of hospital admission (group ILC) or initial antibiotic treatment, followed by delayed laparoscopic cholecystectomy at days 7 to 45 (group DLC). For infection, all patients were treated with moxifloxacin for at least 48 hours. Primary endpoint was occurrence of predefined relevant morbidity within 75 days. Secondary endpoints were as follows: (1) 75-day morbidity using a scoring system; (2) conversion rate; (3) change of antibiotic therapy; (4) mortality; (5) costs; and (6) length of hospital stay. RESULTS: Morbidity rate was significantly lower in group ILC (304 patients) than in group DLC (314 patients): 11.8% versus 34.4%. Conversion rate to open surgery and mortality did not differ significantly between groups. Mean length of hospital stay (5.4 days vs 10.0 days; P < 0.001) and total hospital costs (€2919 vs €4262; P < 0.001) were significantly lower in group ILC. CONCLUSIONS: In this large, randomized trial, laparoscopic cholecystectomy within 24 hours of hospital admission was shown to be superior to the conservative approach concerning morbidity and costs. Therefore, we believe that immediate laparoscopic cholecystectomy should become therapy of choice for acute cholecystitis in operable patients. (NCT00447304).

Vaccination with dendritic cells pulsed with hepatitis C pseudo particles induces specific immune responses in mice.

AIM: To explore dendritic cells (DCs) multiple functions in immune modulation. METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice. Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a single epitope, but the whole "viral surface" induces immunogenicity. For vaccination, mature and activated DC were injected subcutaneously twice. RESULTS: Humoral and cellular immune responses measured by enzyme-linked immunosorbent assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody production as well as T-cells directed against HCV. Furthermore, T-cell responses confirmed two highly immunogenic regions in E1 and E2 outside the hypervariable region 1. CONCLUSION: Our results indicate dendritic cells as a promising vaccination model for HCV infection that should be evaluated further.

Prognostic value of standard parameters as predictors for long-term renal replacement therapy after liver transplantation.

Chronic kidney disease has become increasingly prevalent after liver transplantation (LTPL) because outcome and survival rates have improved. Chronic kidney insufficiency is most likely associated with increased morbidity and mortality. The challenge is to identify patients who will be in need of long-term renal replacement therapy (RRT) after LTPL. We analyzed 208 liver transplant recipients with respect to mortality, associated laboratory values, underlying liver disease, immunosuppressive protocol and the need for RRT. Long-term RRT was defined by the need for RRT 3 months after LTPL. Altogether, 5.8% of the surviving study patients remained in need of RRT 3 months after LTPL. All of these patients continued to need RRT throughout the study period (2 years). The need for RRT significantly increased the 2-year mortality rate 4.3-fold, from 15.4 to 66.7% (p = 0.004). Comparison of laboratory and clinical parameters at the time of LTPL revealed no significant differences for creatinine, albumin and MDRD between patients undergoing hemodialysis 3 months after LTPL and patients without RRT. Comparing mean urea, a difference was observed. However, multivariate regression analyses using easy-to-observe demographic or laboratory parameters failed to generate a model to predict the need for RRT after LTPL. In addition, a comparison of underlying liver disease and immunosuppressive regimes identified no significant differences. Taken together, patients who were on hemodialysis 3 months after LTPL were also on hemodialysis 2 years after LTPL or until death. RRT 3 months after LTPL may predict the risk for chronic renal insufficiency and is associated with significantly increased mortality.

Improved responses to pegylated interferon alfa-2b and ribavirin by individualizing treatment for 24-72 weeks.

BACKGROUND & AIMS: Guidelines recommend that patients with chronic hepatitis C virus (HCV) infection be treated with pegylated interferon and ribavirin for 24, 48, or 72 weeks, based on their virologic response to treatment. We investigated the effects of treating patients for individualized durations. METHODS: We treated 398 treatment-naïve patients who had HCV genotype 1 infections with pegylated interferon alfa-2b and ribavirin for 24, 30, 36, 42, 48, 60, or 72 weeks (mean of 39 weeks, termed individualized therapy); the duration of therapy was determined based on baseline viral load and the time point at which HCV RNA levels became undetectable (measured at weeks 4, 6, 8, 12, 24, and 30). Results were compared with those of 225 patients who received standard treatment for 48 weeks (mean of 38 weeks). RESULTS: Rates of sustained virologic response (SVR) were 55% among patients who received individualized treatment and 48% among those who received standard treatment (P < .0001 for noninferiority). SVR rates, according to the time point at which HCV RNA levels became undetectable, did not differ significantly between groups. Patients with a rapid virologic response (undetectable levels of HCV RNA at week 4) who were treated for 24 to 30 weeks achieved high rates of SVR (86%-88%). Rates of SVR increased among slow responders who first tested negative for HCV RNA at week 24 and were treated for 60 to 72 weeks compared with those treated for 48 weeks (60%-68% vs 43%-44%). The CC polymorphism at IL28B rs129797860 was associated with an increased rate of SVR compared with the CT/TT polymorphism (P < .0001) at baseline but not among patients who had undetectable levels of HCV RNA following treatment. CONCLUSIONS: Individualizing treatment of patients with chronic HCV genotype 1 infections for 24 to 72 weeks results in high rates of SVR among rapid responders and increases SVR among slow responders.

Risk of Confusion: Detection of a Circular Thickness of the Wall in the Lower Part of the Esophagus.

We report a case of a woman with a gastrointestinal bleeding. An esophageal ulcer was detected in the endoscopy, however a histological malignancy could not be found. A computer tomography (CT) scan showed a thickness in the distal esophagus and enlarged lymph nodes, so a malignancy was highly suspected. However, the patient refused to follow the recommended clinical procedure of a surgical intervention. Four years later a carcinoma could be ruled out because of follow-up examinations.

Dendritic cells can effectively be pulsed by HBVsvp and induce specific immune reactions in mice.

Eradication of chronic Hepatitis B virus (HBV) infection, marked by HBs seroconversion, is very rarely achieved by treatment with nucleoside and nucleotide analogs. Therapeutic cell based approaches, like interferon therapy, have a higher chance of seroconversion. Dendritic cells (DC) are key players in the cellular immune response and have been shown to play an important role in controlling HBV infection. In this study, the potential of ex vivo activated DC to induce specific immune responses against HBV was examined. DC derived from bone-marrow of BALB/c or C56BL/6 mice were pulsed with HBV subviral particles (HBVsvp), derived from the HepG2.2.15 cell line. HepG2.2.15 produces subviral particles consisting of the HBc and HBs proteins. Thus, the entire "viral surface" is presented to DC to induce an immune reaction. In vitro pulsation with HBVsvp successfully activated bone-marrow derived DC, demonstrated by FACS analysis showing increased MHCII, CD 86 and CCR-7. Immunization of mice, via subcutaneous injection of the activated DC, induced HBV specific immune reactions which were measured by ELISA, ELISPOT and T-cell proliferation analysis. Vaccination with ex vivo activated DC may be a promising tool for therapeutic or prophylactic approaches against the Hepatitis B virus.

Prevention of adverse drug reactions in intensive care patients by personal intervention based on an electronic clinical decision support system.

OBJECTIVE: We investigated the effect of written drug information for senior clinicians on the incidence of drug-drug interactions (DDIs) and DDI-related adverse events in intensive care patients. DESIGN AND METHODS: A prospective controlled intervention cohort study was conducted in a medical intensive and intermediate care unit in a university hospital. From 1,062 consecutive intensive care patients, those 265 (control: 136, intervention: 129) with > or =8 concurrently prescribed drugs were included in the study (to include high-risk patients with polypharmacy). The DDI information for senior clinicians during an intervention period of 3 months was based on a computerised clinical decision support system (CDSS) containing information on risk and management of 9,453 drug combinations. RESULTS: The number of patients with at least one DDI at the end of the respective study phase decreased by 18% (relative risk reduction) from 90 (66%) patients in controls to 70 (54%) in the intervention group (p = 0.02). The relative risk of a patient suffering from at least one DDI-related adverse event decreased by 43% from 60 (44%) patients in controls to 32 (25%) in the intervention group (p < 0.01). Among these events, the incidence of QT(C) prolongation was reduced by 64% from 15 (11%) patients in the control group to 5 (4%) in the intervention group (p = 0.04), and the incidence of hypokalemia by 80% from 14 (10%) to 2 (2%, p < 0.01). CONCLUSION: Written drug information based on a CDSS considerably decreased DDIs and DDI-related adverse events in routine practice.

Sensitivity and specificity of plasma disappearance rate of indocyanine green as a prognostic indicator in acute liver failure.

BACKGROUND: In patients presenting with acute liver failure (ALF) prediction of prognosis is vital to determine the need of transplantation. Based on the evidence that plasma disappearance rate of indocyanine green (ICG-PDR) correlates with liver cell function, we evaluated the ability of ICG-PDR measured by pulse dye densitometry to predict outcome in patients with acute liver failure. METHODS: Prospectively markers of hepatocellular injury, synthesis and excretion, including ICG-PDR were measured daily until liver transplantation, death, discharge from intensive care unit, or up to 7 days in 25 patients with acute liver failure. Receiver operating curve (ROC) analysis was performed to assess the value of ICG-PDR to predict outcome in ALF. RESULTS: The 25 patients analyzed included 18 that recovered spontaneously and 7 that underwent liver transplantation (n = 6) or died (n = 1). Causes of ALF included viral hepatitis (n = 4), toxic liver injury (n = 15), ischemic liver injury (n = 2), and cryptogenic liver failure (n = 4). King's college criteria were fulfilled in 85.7% of patients not recovering spontaneously and in 16.7% of patients recovering spontaneously. The mean ICG-PDR measured on day 1 in patients recovering spontaneously was 12.0 +/- 7.8%/min and in patients not recovering spontaneously 4.3 +/- 2.0%/min (P = 0.002). By ROC analysis the sensitivity and specificity of an ICG-PDR value

Liver transplantation in HIV-positive patients.

Death from end-stage liver disease (ESLD) because of chronic hepatitis B and C has become an increasing problem in human immunodeficiency virus (HIV)-infected patients in the last years. This is mainly because of the dramatic decrease of HIV-related morbidity and mortality since the introduction of highly active antiretroviral therapy (HAART). Although the data on the outcome of liver transplantation in HIV-infected recipients with ESLD is limited, overall results seem comparable to non-HIV-infected recipients. Therefore, liver transplant centres around the world are increasingly accepting HIV-infected individuals as organ recipients. Post-transplantation control of HIV replication is achieved by continuing HAART. As in non-HIV-infected patients, hepatitis B virus recurrence is efficiently prevented by hepatitis B immunoglobulin and antiviral therapy. Re-infection of the allograft with hepatitis C virus, however, remains an important problem, and progress to allograft cirrhosis may even be more rapid than in HIV-negative patients. Interactions in drug metabolism between the HAART components and the immunosuppressive drugs are difficult to predict and require close monitoring of drug levels and dose adjustments. The complexity in this setting makes close cooperation between transplant surgeons, hepatologists, HIV-clinicians and pharmacologists mandatory. As experience on liver transplantation in HIV-infected individuals is still limited, to date results from large prospective trials addressing key issues are needed.

Tissue penetration of moxifloxacin into human gallbladder wall in patients with biliary tract infections.

OBJECTIVES: Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication. PATIENTS AND METHODS: Hospitalized patients with acute cholecystitis received a single, 1 h infusion of 400 mg of moxifloxacin before cholecystectomy. Serum and gallbladder wall tissue samples were collected during surgery, and the moxifloxacin concentrations were measured by HPLC. RESULTS: Sixteen patients (eight men and eight women) were included between January 2007 and April 2008. The time between start of infusion and gallbladder removal ranged from 50 min to 21 h 10 min. The serum concentration at the time of cholecystectomy was between 0.39 and 4.37 mg/L, and the tissue concentration between 1.73 and 17.08 mg/kg. The tissue-to-serum concentration ratio ranged from 1.72 to 6.33. CONCLUSIONS: The results show that moxifloxacin penetrates well into gallbladder tissue and is therefore a therapeutic option for biliary tract infection. The highest concentrations in serum and gallbladder tissue were measured shortly after the end of a 1 h infusion. As perioperative prophylaxis, moxifloxacin should therefore be administered 30-60 min before the first surgical incision.

Low levels of prothrombin time (INR) and platelets do not increase the risk of significant bleeding when placing central venous catheters.

BACKGROUND AND PURPOSE: Central venous catheters are frequently placed in intensive care medicine for multiple indications. The risk of severe bleeding after cannulation is considered to be increased in patients with abnormal coagulation, common in critically ill patients. PATIENTS AND METHODS: This open prospective trial, performed at two medical intensive care units and one hematology intermediate care ward, investigated whether insertion of a central venous catheter in patients with coagulopathy (prothrombin time or= 1.5] and/or platelets

A single-center experience of 500 liver transplants using the modified piggyback technique by Belghiti.

Over the past 4 decades, the surgical techniques of liver transplantation (LTx) have permanently evolved and been modified. Among these, the modified piggyback (MPB) technique by Belghiti offers specific advantages. The objective of this study was to present our single-center experience with the MPB technique in 500 cases. Recipients' perioperative data were prospectively collected and evaluated. Postoperative and specific complications, stay in the intensive and intermediate care unit, and the mortality rate with cause of death were analyzed. Most recipients were classified as Child C (49.1%). For the patients who underwent LTx for the first time, alcoholic (23.9%) and viral (22.2%) cirrhosis and hepatocellular carcinoma (15.1%) were the prevalent indications. The overall median warm ischemia time, anastomosis duration, and operative time were 45, 108, and 320 minutes, respectively. The median intraoperative blood loss was 1500 mL. A venovenous bypass was never needed to maintain hemodynamic stability. Only in a few cases was temporary inferior vena cava clamping necessary. Most prominent surgical complications were hemorrhage, hematoma, and wound dehiscence. Renal failure occurred in 6.2% of patients. The overall median stay in the intensive and intermediate care unit was 14 days. The mortality rates within 30 and 90 days were 6.3% and 13.3%, respectively. No technique-related death occurred. The MPB technique by Belghiti is a feasible and simple LTx technique. The caval flow is preserved during the anhepatic phase, and this minimizes the need for venovenous bypass or portocaval shunt. This technique requires only 1 caval anastomosis, which is easy to perform with a short anhepatic phase. To minimize the risk of outflow obstruction, attention should be paid by doing a wide cavocavostomy cranially to the donor inferior vena cava in a door-lock manner. This technique can be applied in almost all patients undergoing LTx for the first time and liver retransplantation as well.

Pro-active provision of drug information as a technique to address overdosing in intensive-care patients with renal insufficiency.

PURPOSE: To correct overdosing of drugs requiring adjustment based on renal function in intensive-care patients. METHODS: In a prospective intervention study, we estimated individual glomerular filtration rate and assessed whether medication required dose adjustment based on renal function. Senior clinicians received a structured report containing recommendations as to whether and how to adjust dosage in the individual patient (intervention). Prevalence of overdosed drugs (primary outcome), extent of overdoses, and reasons for nonacceptance of recommendations (secondary outcomes) were assessed. RESULTS: Of 138 screened intensive-care patients, 68 (49%) had renal impairment, and 110 (14%) of the 805 prescribed drugs required consideration of renal function. A potential overdose was found in 53/110 drugs (48%) and this rate decreased to 26/110 (24%, P < 0.001) after the intervention. The average extent of overdose was reduced from 54% before to 31% after the intervention (P < 0.001). The main reasons expressed by the physicians for nonacceptance of recommendations were a large therapeutic index or minor overdoses of the involved drugs. CONCLUSIONS: In intensive-care patients, overdosing of drugs requiring adjustment based on renal function is still very common. Drug information counselling significantly decreased the prevalence and extent of overdose.

Adverse drug reactions and deliberate self-poisoning as cause of admission to the intensive care unit: a 1-year prospective observational cohort study.

OBJECTIVE: The aim of the present study was (1) to determine the prevalence of intensive care unit (ICU) admissions due to an adverse drug reaction (ADR), and (2) to compare affected patients with patients admitted to the ICU for the treatment of deliberate self-poisoning using medical drugs. DESIGN: Prospective observational cohort study. SETTING: Fourteen bed medical ICU including an integrated intermediate care (IMC) section at a tertiary referral center. PATIENTS: A total of 1,554 patients admitted on 1 January 2003 to 31 December 2003. RESULTS: Ninety-nine patients were admitted to the ICU with a diagnosis of ADR (6.4% of all admissions), 269 admissions (17.3%) were caused by deliberate self-poisoning. Patients admitted for treatment of ADR had a significantly higher age, a longer treatment duration in the ICU, a higher SAPS II score, and a higher 6-month mortality than those with deliberate self-poisoning. Most patients (71.7%) suffering from ADR required advanced supportive care in the ICU while the majority of patients (90.7%) with deliberate self-poisoning could be sufficiently treated in the IMC area. All diagnostic and therapeutic procedures in the ICU except mechanical ventilation were significantly more often performed in patients with ADR. CONCLUSIONS: This study provides further evidence that ADR is a frequent cause of admission to medical ICUs resulting in a considerable use of ICU capacities. In the present setting patients with ADR required longer and more intense medical treatment in the ICU than those with deliberate self-poisoning.

CT and endoscopic ultrasound in comparison to endoluminal MRI: preliminary results in staging gastric carcinoma.

PURPOSE: To prospectively compare diagnostic parameters of a newly developed endoluminal MRI (endo-MRI) concept with endoscopic ultrasound (EUS) and hydro-computer tomography (Hydro-CT) in T-staging of gastric carcinoma on one patient collective. MATERIAL AND METHODS: 28 consecutive patients (11 females, 17 males, age range 46-87 years, median 67 years) referred for surgery due to a gastric malignancy were included. Preoperative staging by EUS was performed in 14 cases and by Hydro-CT in 14 cases within a time frame of 2 weeks. Ex vivo endo-MRI examination of gastric specimens was performed directly after gastrectomy within a time interval of 2-3h. EUS data were acquired from the clinical setting whereas Hydro-CT and endo-MRI data were evaluated in blinded fashion by two experienced radiologists and one surgeon well experienced in EUS on gastric carcinomas. RESULTS: Histopathology resulted in 4 pT1, 17 pT2, 3 pT3 and 2 pT4 carcinomas with 2 gastric lymphomas which were excluded. Overall accuracy for endo-MRI was 75% for T-Staging of the 26 carcinomas. EUS achieved 42.9% accuracy; endo-MRI in this subgroup was accurate in 71.4%. Hydro-CT was correct in 28.6%, accuracy for endo-MRI in this subgroup was 71.4%. CONCLUSION: The direct comparison of all three modalities on one patient collective shows that endo-MRI is able to achieve adequate staging results in comparison with clinically accepted methods like EUS and Hydro-CT in classifying the extent of tumor invasion into the gastric wall. However the comparison is limited as we compared in vivo routine clinical data with experimental ex vivo data. Future investigations need to show if the potential of endo-MRI can be transferred into a clinical in vivo setting.

Admission to intensive care for parasuicide by self-poisoning: variation by time cycles, climate and the lunar cycle.

The aim of this study was to characterize patients after self-poisoning with suicidal intent regarding age, sex and type of substances ingested, as well as to identify temporal variations of attempted suicides and associations with climate variables and the lunar cycle. During the years 2002-2004, a total of 691 patients were admitted for self-poisoning parasuicides. The male to female ratio was 1:1.65 with mean ages of 39 and 37 years, respectively. Benzodiazepines and antidepressants were the most frequently taken substances. A significant variation with the time of the day with a peak before midnight was observed for both sexes. Variation with the day of the week was less clear and showed a peak incidence for parasuicides on Mondays. There was no significant variation with the monthly or annual cycle. The frequency of parasuicides was associated with "bad weather" (precipitation). No association of parasuicide incidences to the lunar cycle was observed.

Prevention of intravenous drug incompatibilities in an intensive care unit.

PURPOSE: The frequency of drug administration errors and incompatibilities between intravenous drugs before and after an intervention in an intensive care unit (ICU) is discussed. METHODS: Critically ill adult patients with intoxications, multiorgan failure, and serious infections were included in a retrospective analysis and in a prospective two-period, one-sequence study. In the retrospective analysis, the most frequent brands of i.v. medications used in the ICU of a gastroenterologic department in a teaching hospital were identified. All possible combinations and resulting incompatibilities were defined. Based on the results, a standard operating procedure (SOP) was established to prevent frequent and well-documented incompatibilities among i.v. medications. In the prospective study, trained pharmacy students assessed incompatible coinfusions before and after SOP implementation. RESULTS: In the retrospective analysis of 100 patients, 3617 brands of drug pairs were potentially given concurrently through one i.v. line and 7.2% of the drug pairs were incompatible. Antibiotics, such as piperacillin-tazobactam and imipenem-cilastatin, were the most frequent incompatible drug pairs. The newly developed SOP mandated that administration of these drugs be separated from all other drugs and suggested the use of an idle i.v. line for infusion whenever possible. In the prospective study of 50 patients, the frequency of incompatible drug pairs was reduced by the time of intervention from 5.8% to 2.4%. Incompatible drug pairs that were governed by the new SOP were reduced from 1.9% to 0.5%. CONCLUSION: Administration of incompatible i.v. drugs in critically ill patients was frequent but significantly reduced by procedural interventions with SOPs.