Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care--short version.

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2(nd) Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%). Between 2006-2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3(rd) Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade "A" (very strong recommendation), Grade "B" (strong recommendation) and Grade "0" (open recommendation) were agreed. As a result of this process we now have an interdisciplinary and consensus-based set of 3(rd) Generation Guidelines that take into account all critically illness patient populations. The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.

Presence of cytokeratins in exhaled breath condensate of mechanical ventilated patients.

Exhaled breath condensate (EBC) contains small amounts of protein leaving the lung by aerosol droplet generation. Protein patterns in EBC might be useful in monitoring acute and severe pulmonary disease and in particular monitoring of mechanical stress during ventilation. EBC (10ml) was collected from 30 ventilated patients with respiratory failure including 24 patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and from 10 healthy volunteers. Samples were analyzed using gel electrophoresis. Bands were characterized by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). In the EBC of mechanically ventilated patients 53.3% exhibited three bands (50-70kDa), 26.7% two bands, 10% one band, and 10% had no bands. While no bands were detected in volunteers EBC. MALDI-TOF analysis identified these bands as cytokeratins 2, 9 and 10. Cytokeratins 2 and 10 were confirmed by Western blot. The detection rate of cytokeratins was correlated to peak inspiratory pressure, positive endexpiratory pressure and ARDS score, but not with inflammatory markers or smoking status. Cytokeratins are present in EBC of mechanically ventilated patients. A strong correlation with parameters of ventilatory stress, such as increased distension, presence of lung injury and time of ventilation suggests a relation with ventilator-associated damage to the pulmonary parenchyma.

Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock.

OBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. DESIGN: Prospective randomized, placebo-controlled, multiple-center trial. SETTING: Eleven intensive care units in Germany. PATIENTS: Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. INTERVENTIONS: Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. CONCLUSIONS: The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.

ST-segment recovery and prognosis in patients with ST-elevation myocardial infarction reperfused by prehospital combination fibrinolysis, prehospital initiated facilitated percutaneous coronary intervention, or primary percutaneous coronary intervention.

Complete ST-segment recovery (STR) is associated with favorable prognosis in ST-elevation myocardial infarction (STEMI). The optimal reperfusion strategy in patients presenting soon after symptom onset is still a matter of debate. STR for patients treated by prehospital combination fibrinolysis or prehospital initiated facilitated percutaneous coronary intervention (PCI) compared with primary PCI has not been assessed. In the Leipzig Prehospital Fibrinolysis Study, patients with STEMI (symptoms <6 hours) were randomized to prehospital combination fibrinolysis (1/2 dose reteplase + abciximab; n = 82, group A) or prehospital initiated facilitated PCI (n = 82, group B). Further, a control group of patients with primary PCI (n = 136, group C) was prospectively assessed. STR at 90 minutes was analyzed by blinded observers as percent resolution. Categorization was performed as complete resolution (>70%), intermediate resolution (70% to 30%), or no resolution (<30%). The percentage of patients with complete STR was highest in group B with 80% versus 52% in group A and 52% in group C (p <0.001, B vs A and C, p = NS; A vs C). Complete STR resulted in lower event rates for the combined clinical end point of death, myocardial reinfarction, and stroke compared with intermediate and no STR in groups A (complete 9.8%, intermediate 23.8%, no STR 36.8%, p = 0.04), B (7.7%, 18.2%, and 50.0%, p = 0.01), and C (8.6%, 18.4%, and 42.9%, p <0.001). In conclusion, prehospital initiated facilitated PCI results in the highest percentage of complete STR compared with prehospital combination fibrinolysis or primary PCI. In addition, STR has been confirmed to predict prognosis in timely optimized reperfusion strategies.

The effect of different anticoagulants on thrombin generation.

Decrease in thrombin generation is the key effect in anticoagulation. The aim of the present study was to investigate the effect of anticoagulants on thrombin generation and the relation to platelet count. Plasma samples from 10 healthy volunteers (mean age 43.0 +/- 9 years) were incubated at preset platelet counts with different doses of the anticoagulants lepirudin, fondaparinux and low molecular weight heparins. Thrombin generation was measured in a tissue factor-mediated assay using a fluorometer and a slow-reacting fluorogenic substrate. The endogenous thrombin potential, the lag phase, the maximum reaction velocity (Vmax) and the concentration of a given anticoagulant required for 50% inhibition of thrombin generation (IC50) are presented. All three anticoagulants decreased endogenous thrombin potential and prolonged the lag phase in a dose-dependent manner. Fondaparinux and low molecular weight heparins, but not hirudin, decreased Vmax in a concentration-dependent manner. With increasing platelet count, the IC50 increased but the extent of this increase was not uniform for the three anticoagulants and the three variables investigated. The influence of anticoagulants on thrombin generation is variable, depending on their basic mechanism of action. In defining and comparing their effects, the endogenous thrombin potential, the lag phase and the maximum reaction velocity should be considered together. Platelets have a considerable influence on the magnitude of thrombin generation.

Enteral nutrition delivery and energy expenditure in medical intensive care patients.

BACKGROUND AND AIMS: Delivery of enteral nutrition (EN) in critical illness is often inadequate. This prospective observational study addresses the implementation of enteral feeding in critically ill medical patients and its relation to energy expenditure. METHODS: All admissions to a university medical ICU over a period of one year were screened. Patients receiving EN for at least 7 days were followed up. The caloric target was a minimum of 20 kcal/kg/day. The feeding volume was increased daily by 500 ml and a maximum of 2000 ml/day was targeted to be achieved by day 4 of admission. Energy expenditure was measured with indirect calorimetry on day 3 or 5. RESULTS: Two hundred and thirtyone patients required artificial nutrition, of which 61 patients were enterally fed for 7 days. This group was followed for a total of 750 feeding days. The gastric route was used at the start, with a post-pyloric feeding required during follow-up in 36.1% of patients due to high gastric residual. EN was interrupted in 32.1% of the feeding days. The daily administered volume was 86.2 +/- 30.4% of the prescribed. The mean enteral caloric supply in relation to energy expenditure was between 39.2 +/- 34.6% on day 1 and 83.1 +/- 31.1% on day 6. The targeted maximum feed volume was achieved on day 4 in 75.4% of the patients. Patients with a delayed target time had a higher mortality rate than those with a target time of <4 days (73.3% vs. 26.1%), CONCLUSIONS: A high delivery-to-prescription rate could be achieved with a standardized enteral feeding protocol in critically ill medical patients. However, caloric delivery is much less than measured energy expenditure. Enteral feeding intolerance is associated with a high mortality rate.

Exhaled breath condensate cytokine patterns in chronic obstructive pulmonary disease.

Differences in cytokine patterns in stable chronic obstructive pulmonary disease (COPD), exacerbated COPD, smokers without apparent COPD, and healthy volunteers should be of interest for pathophysiological and therapeutic reasons. Methods including lavage, biopsy and sputum have been employed to investigate cytokines in the lung. For asystematic comparison, exhaled breath condensate (EBC) appears to be well suited. We investigated healthy volunteers, smokers without apparent COPD, stable and exacerbated COPD patients (+/- inhalative steroids) and finally those whose exacerbation made mechanical ventilation inevitable, for a more complete picture of inflammatory cytokines in COPD. We chose EBC because it is non-invasive and can be used repeatedly in spontaneous breathing individuals and during mechanical ventilation. EBC cytokines (IL-1 beta, IL-6, IL-8, IL-10, IL-12 p 70, TNF-alpha) were assayed from a single sample using a multiplex array test kit. We observed a significant increase of all cytokines in acute exacerbation compared to stable COPD, smokers, and volunteers. Stable COPD and volunteers exhibited only small differences in cytokine pattern with respect to IL-1 beta and IL-12 (P<0.01). Smokers had increased levels of all investigated cytokines (P<0.01) compared to non-smokers and, with the exception of IL-1 beta, to stable COPD. Inhaled steroids resulted in reduced levels of IL-1 beta, IL-6, IL-8, IL-10, and IL-12 (all: P<0.01) in stable COPD (all: ex-smokers) with dose dependency for IL-8, IL-1 beta and IL-12. EBC analysis successfully characterized important differences in stable COPD compared to exacerbation or smoking and non-smoking healthy individuals.

Comparison of pre-hospital combination-fibrinolysis plus conventional care with pre-hospital combination-fibrinolysis plus facilitated percutaneous coronary intervention in acute myocardial infarction.

AIMS: Early and complete reperfusion is the main treatment goal in ST-elevation myocardial infarction (STEMI). The timely optimal reperfusion strategy might be a pre-hospital initiated pharmacological reperfusion with subsequent facilitated percutaneous coronary intervention (PCI). This approach has been compared with pre-hospital combination-fibrinolysis only to determine whether either one of these methods offer advantages with respect to final infarct size. METHODS AND RESULTS: Patients with STEMI were randomized to either pre-hospital combination-fibrinolysis (half-dose reteplase+abciximab) with standard care (n=82) or pre-hospital combination-fibrinolysis with facilitated PCI (n=82). Primary endpoint was the infarct size assessed by delayed enhancement magnetic resonance. Secondary endpoints were ST-segment resolution at 90 min and a composite of death, re-myocardial infarction, major bleeding, and stroke at 6 months. The infarct size was lower after facilitated PCI with 5.2% [interquartile range (IQR) 1.3-11.2] as opposed to 10.4% (IQR 3.4-16.3) after pre-hospital combination-fibrinolysis (P=0.001). Complete ST-segment resolution was 80.0% after facilitated PCI vs. 51.9% after pre-hospital combination-fibrinolysis (P<0.001). After facilitated PCI, there was a trend towards a lower event rate in the combined clinical endpoint (15 vs. 25%, P=0.10, relative risk 0.57, 95% CI 0.28-1.13). CONCLUSION: In patients with STEMI, additional facilitated PCI after pre-hospital combination-fibrinolysis results in an improved tissue perfusion with subsequent smaller infarct size as opposed to pre-hospital combination-fibrinolysis alone. This translates into a trend towards a better clinical outcome.

The endogenous thrombin potential and high levels of coagulation factor VIII, factor IX and factor XI.

High plasma concentrations of factor VIII, factor IX and factor XI have been reported as thrombosis risk factors. Using the thrombin generation test in platelet-poor plasma, it was aimed to describe the mechanism for this increased thrombosis risk. Endogenous thrombin potential was measured in platelet-poor plasma in 180 patients with a history of thromboembolism, and results were compared with those of 180 age-matched and sex-matched controls. Subjects with major hereditary and acquired thrombophilia were excluded. Plasma concentrations of the clotting factor VIII, factor IX and factor XI were significantly elevated in patients compared with controls. The mean endogenous thrombin potential was significantly higher in patients than in controls: 191.3 +/- 3.1 (95% confidence interval, 185.3-197.4) arbitrary units versus 180.8 +/- 2.6 (95% confidence interval, 175.7-185.9) arbitrary units (P = 0.009). The endogenous thrombin potential was significantly higher in patients with elevated factor IX and factor XI, but elevated factor VIII was not associated with a significant increase in endogenous thrombin potential. In conclusion, the increased thrombosis risk associated with high plasma concentrations of factor IX and factor XI may be explained by the increase in endogenous thrombin potential. However, this did not help explain the association between elevated factor VIII and thrombosis risk.

Exhaled breath condensate acidification in acute lung injury.

Lung injury in ventilated lungs may occur due to local or systemic disease and is usually caused by or accompanied by inflammatory processes. Recently, acidification of exhaled breath condensate pH (EBC-pH) has been suggested as marker of inflammation in airway disease. We investigated pH, ammonia, Lactate, pCO2, HCO3-, IL-6 and IL-8 in EBC of 35 ventilated patients (AECC-classification: ARDS: 15, ALI: 12, no lung injury: 8). EBC-pH was decreased in ventilated patients compared to volunteers (5.85 +/- 0.32 vs. 7.46 +/- 0.48; P < 0.0001). NH4+, lactate, HCO3-, pCO2, IL-6 and IL-8 were analyzed in EBC and correlated with EBC-pH. We observed correlations of EBC-pH with markers of local (EBC IL-6: r = -0.71, P < 0.0001, EBC IL-8: r = -0.68, P < 0.0001) but not of systemic inflammation (serum IL-6, serum IL-8) and with indices of severity of lung injury (Murray's Lung Injury Severity Score; r = -0.73, P < 0.0001, paO2/FiO2; r = 0.54, P < 0.001). Among factors potentially contributing to pH of EBC, EBC-lactate and EBC-NH4+ were found to correlate with EBC-pH. Inflammation-induced disturbances of regulatory mechanisms, such as glutaminase systems may result in EBC acidification. EBC-pH is suggested to represent a marker of acute lung injury caused by or accompanied by pulmonary inflammation.

Thrombin generation in severe haemophilia A and B: the endogenous thrombin potential in platelet-rich plasma.

Thrombin generation was investigated in platelet-rich plasma (PRP) from 11 healthy controls, 17 patients with severe haemophilia A and 7 patients with severe haemophilia B. Mean endogenous thrombin potential (ETP) in arbitrary fluorescence units (FU) was 226.9 +/- 44.6, 186.4 +/- 22.5, 154.2 +/- 41.3 in controls, haemophilia A and B, respectively, all at a platelet count of 200 x 10(9)/l (p = 0.004 for controls vs. haemophilia A, p = 0.003 for controls vs. haemophilia B, no significant difference between haemophilia A and B). The contribution of FVIII to thrombin generation in haemophilia A was 1.31 +/- 0.16 FU/% of FVIII:C activity, while for FIX in haemophilia B this was 0.80 +/- 0.21 FU/% of FIX activity. There was an almost linear relationship between increasing platelet count and thrombin generation up to a mean platelet count of 100 x 10(9)/l. Further increase in platelet count has only a marginal influence on thrombin generation. Platelets increase ETP in haemophilia A by 0.184 +/- 0.022 FU/10(9) platelets/l and in haemophilia B by 0.319 +/- 0.085 FU/10(9) platelets/l, and this was significantly different between the two groups (p = 0.0002). This influence of plate-lets diminishes with increasing concentration of either FVIII or FIX. In conclusion, there is a difference in thrombin generation between haemophilia A and B, and this may be attributed to the role of platelets in the assembly of the tenase complex on their surface.

Is there a place for thyroidectomy in older patients with thyrotoxic storm and cardiorespiratory failure?

Early thyroidectomy is the treatment of choice for thyrotoxic storm in patients with thyroid autonomy often induced by iodine. However, older patients who are mostly affected by this condition often have underlying chronic cardiopulmonary diseases, apparently contradicting surgical intervention. The published evidence for suitable treatment strategies in these patients is limited. We report the outcome of a series of older critically ill patients who were treated by thyroidectomy because of thyrotoxic storm. We retrospectively analyzed the outcome of 10 patients (4 males, 6 females; 70 years of age, range, 54-79, Burch-Wartofsky point scale, 61; range, 40-85) with thyrotoxic storm, thyroid autonomy, and severe cardiorespiratory and renal failure with cardiac arrhythmia, coronary artery or chronic obstructive pulmonary disease, or acute inflammation. Thyroidectomy was performed for the following reasons: symptoms of thyrotoxic storm deteriorated or did not improve within 24-48 hours despite intensive medical treatment, or patients developed thionamide-induced agranulocytosis or severe thrombocytopenia. All patients with severe accompanying diseases survived thyroidectomy (early post-operative mortality, 0%). The two oldest patients died 2-3 weeks after thyroidectomy because of myocardial infarction or respiratory failure (late postoperative mortality, 20%). In contrast, in the few previous reports of patients who underwent thyroidectomy for thyrotoxic storm and severe accompanying diseases (n = 7), late postoperative mortality was 43%. The overall mortality for all reported patients including our own, who underwent thyroidectomy for thyrotoxic storm with and without severe accompanying disease (n = 49) was 10%. Our results suggest that early total thyroidectomy should be considered as the method of choice for older, chronically ill patients with thyrotoxic storm complicated by cardiorespiratory and renal failure, especially if high-dose thionamide treatment, iopanoic acid, glucocorticoids, and intensive care fail to improve the patient's conditions within 12-24 hours.

Exhaled breath condensate nitrite and its relation to tidal volume in acute lung injury.

STUDY OBJECTIVE: Mechanical ventilation may damage the lung. Low tidal volume (VT) is protective, but VT is scaled to body weight (BW) and may be high in functionally small ARDS lungs. We hypothesized that exhaled breath condensate (EBC) nitrite (NO(2)(-)) concentration may increase with lung distension. DESIGN: Prospective, noncontrolled study. SETTING: University hospital and medical ICU. PATIENTS: Thirty-five ICU patients requiring mechanical ventilation (severe pneumonia, n = 31; exacerbated COPD, n = 4). Patients were scored according to American and European Consensus Conference on ARDS criteria (AECC) [no lung injury, n = 7; acute lung injury, n = 13; ARDS, n = 15], as well as the Murray lung injury severity score (LISS) [score 0, n = 3; score 0.1 to 2.5, n = 19; score > 2.5, n = 13]. INTERVENTIONS: EBC was collected and analyzed for NO(2)(-), interleukin (IL)-6, and IL-8. Serum was analyzed for IL-6, IL-8, and procalcitonin. RESULTS: and measurements: EBC NO(2)(-) correlated well with VT (milliliters per kilogram of BW; r = 0.79, p < 0.0001) and expiratory minute volume (r = 0.60, p < 0.0001) but not with other ventilatory parameters or parameters of pulmonary (EBC IL-6, EBC IL-8) or systemic (serum IL-6, IL-8, and procalcitonin) inflammation. The ratio of EBC NO(2)(-) and the size of the VT correlated directly with lung injury (AECC, r = 0.66, p < 0.0001; LISS, r = 0.84, p < 0.0001). CONCLUSION: EBC NO(2)(-) increased linearly with VT. The ratio of EBC NO(2)(-) to VT is assumed to reflect NO(2)(-) release at a given VT. An increase in this ratio indicates an inappropriate increase of NO(2)(-) production most likely due to mechanical stress of the remaining open lung units in injured lungs. We conclude that the EBC NO(2)(-)/VT ratio may help to identify situations of critical mechanical stress.

Adrenocortical hormones in survivors and nonsurvivors of severe sepsis: diverse time course of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol.

OBJECTIVE: Activation and suppression of immune responses are crucial events during sepsis. Based on substantial new data, a complex picture of differential immune-enhancing and immunosuppressive actions of adrenocortical steroids is emerging. The adrenal androgen dehydroepiandrosterone and its precursor, dehydroepiandrosterone-sulfate, show a considerable decrease with increasing age and serve as functional antagonists to endogenous glucocorticoids. Therefore, we examined time-dependent changes in dehydroepiandrosterone, dehydroepiandrosterone-sulfate, cortisol, adrenocorticotropin, and inflammatory variables in surviving and nonsurviving patients with severe sepsis. DESIGN: Prospective observational study in consecutive patients. SETTING: Medical and interdisciplinary intensive care units in two university hospitals and one city hospital. PATIENTS: Thirty nonsurgical patients (25 men and 5 women) with severe sepsis (American College of Chest Physicians/Society of Critical Care Medicine criteria); 15 survivors (mean age, 54 +/- 14 yrs; Acute Physiology and Chronic Health Evaluation III score, 59 +/- 35) and 15 nonsurvivors (mean age, 63 +/- 15 yrs; Acute Physiology and Chronic Health Evaluation III score, 67 +/- 24) were included. Hormones were compared individually and between survivors/nonsurvivors by sequential blood drawings from early sepsis till time of recovery/death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During early sepsis, cortisol (nmol/L) was not significantly higher in survivors than nonsurvivors (750 +/- 121 vs. 454 +/- 92, p <.08) and decreased in survivors (p <.01) during late sepsis. During early sepsis, dehydroepiandrosterone-sulfate (percentage of age-matched normal levels) was higher in survivors than nonsurvivors (85 +/- 19 vs. 22 +/- 7, p <.01). Dehydroepiandrosterone-sulfate decreased in survivors (p =.0001) but remained low in nonsurvivors during late sepsis. Dehydroepiandrosterone (percentage of age-matched normal levels) was not significantly elevated in survivors compared to nonsurvivors during early sepsis (282 +/- 42 vs. 214 +/- 63, p <.08). Dehydroepiandrosterone decreased in survivors (p <.01) but not in nonsurvivors during late sepsis. Linear regression for dehydroepiandrosterone levels showed a reconstitution of age dependence only in survivors during recovery. Adrenocorticotropin levels did not change. The dehydroepiandrosterone-sulfate/cortisol ratio decreased significantly in both survivors and nonsurvivors, whereas dehydroepiandrosterone/cortisol ratio only decreased in survivors during course of sepsis. CONCLUSIONS: During sepsis, adrenal androgens and glucocorticoids show a diverse time-dependent course in survivors and nonsurvivors.

Human experience with transvenous biventricular defibrillation using an electrode in a left ventricular vein.

This study investigated the safety and feasibility of transvenous biventricular defibrillation in ICD patients. Some patients may have high DFTs due to weak shock field intensity on the LV. Animal studies showed a LV shocking electrode dramatically lowered DFTs. This approach might benefit heart failure patients already receiving a LV lead or conventional ICD patients with high DFTs. A modified guidewire was used as a temporary left venous access defibrillation electrode (LVA lead). In 24 patients receiving an ICD, the LVA lead was advanced through a guide catheter in the coronary sinus (CS) and into a randomized LV vein (anterior or posterior) using a venogram for guidance. Paired DFT testing compared a standard right ventricular defibrillation system to a biventricular defibrillation system. There were no complications or adverse events. As randomized, LVA lead insertion success was 87% and 71% for anterior and posterior veins, respectively, and 100% after crossover. Total insertion process time included venogram time (32.5 +/- 26.9 minutes, range 5-115, mode 15 minutes) and LVA lead insertion time (15 +/- 14 minutes, range 1-51, mode 7 minutes). An apical LVA lead position was achieved in 11 (45%) of 24 patients and 7 (64 %) of these 11 displayed a DFT reduction; however, mean DFTs were not statistically different. Transvenous biventricular defibrillation is feasible and was safe under the conditions tested. Additional clinical studies are justified to determine if optimized LV lead designs, lead placement, and shock configurations can yield the same large DFT reductions as observed in animals.