Intravenous versus inhalation anaesthesia for one-lung ventilation

BackgroundThis is an update of a Cochrane Review first published in The Cochrane Library, Issue 2, 2008.The technique called one-lung ventilation can confine bleeding or infection to one lung, prevent rupture of a lung cyst or, more commonly, facilitate surgical exposure of the unventilated lung. During one-lung ventilation, anaesthesia is maintained either by delivering an inhalation anaesthetic to the ventilated lung or by infusing an intravenous anaesthetic. It is possible that the method chosen to maintain anaesthesia may affect patient outcomes. Inhalation anaesthetics may impair hypoxic pulmonary vasoconstriction (HPV) and increase intrapulmonary shunt and hypoxaemia.ObjectivesThe objective of this review was to evaluate the effectiveness and safety of intravenous versus inhalation anaesthesia for one-lung ventilation.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library (2012, Issue 11); MEDLINE (1966 to November 2012); EMBASE (1980 to November 2012); Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS, 1982 to November 2012) and ISI web of Science (1945 to November 2012), reference lists of identified trials and bibliographies of published reviews. We also contacted researchers in the field. No language restrictions were applied. The date of the most recent search was 19 November 2012. The original search was performed in June 2006.Selection criteriaWe included randomized controlled trials and quasi-randomized controlled trials of intravenous (e. g. propofol) versus inhalation (e. g. isoflurane, sevoflurane, desflurane) anaesthesia for one-lung ventilation in both surgical and intensive care participants. We excluded studies of participants who had only one lung (i.e. pneumonectomy or congenital absence of one lung).Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.Main resultsWe included in this updated review 20 studies that enrolled 850 participants, all of which assessed surgical participants no studies investigated one-lung ventilation performed outside the operating theatre. No evidence indicated that the drug used to maintain anaesthesia during one-lung ventilation affected participant outcomes. The methodological quality of the included studies was difficult to assess as it was reported poorly, so the predominant classification of bias was 'unclear'.Authors' conclusionsVery little evidence from randomized controlled trials suggests differences in participant outcomes with anaesthesia maintained by intravenous versus inhalational anaesthesia during one-lung ventilation. If researchers believe that the type of drug used to maintain anaesthesia during one-lung ventilation is important, they should design randomized controlled trials with appropriate participant outcomes, rather than report temporary fluctuations in physiological variables.

Pilates in Heart Failure Patients: A Randomized Controlled Pilot Trial

Background: Conventional cardiac rehabilitation program consist of 15 min of warm-up, 30 min of aerobic exercise and followed by 15 min calisthenics exercise. The Pilates method has been increasingly applied for its therapeutic benefits, however little scientific evidence supports or rebukes its use as a treatment in patients with heart failure (HF). Purpose: Investigate the effects of Pilates on exercise capacity variables in HF. Methods: Sixteen pts with HF, left ventricular ejection fraction 27 +/- 14%, NYHA class III were randomly assigned to conventional cardiac rehabilitation program (n = 8) or mat Pilates training (n = 8) for 16 weeks of 30 min of aerobic exercise followed by 20 min of the specific program. Results: At 16 weeks, pts in the mat Pilates group and conventional group showed significantly increase on exercise time 11.9 +/- 2.5 to 17.8 +/- 4 and 11.7 +/- 3.9 to 14.2 +/- 4 min, respectively. However, only the Pilates group increased significantly the ventilation (from 56 +/- 20 to 69 +/- 17 L/min, P= 0.02), peak VO2 (from 20.9 +/- 6 to 24.8 +/- 6 mL/kg/min, P= 0.01), and O-2 pulse (from 11.9 +/- 2 to 13.8 +/- 3 mL/bpm, P= 0.003). The Pilates group showed significantly increase in peak VO2 when compared with conventional group (24.8 +/- 6 vs. 18.3 +/- 4, P= 0.02). Conclusions: The result suggests that the Pilates method may be a beneficial adjunctive treatment that enhances functional capacity in patients with HF who are already receiving standard medical therapy.

Low mechanical ventilation times and reintubation rates associated with a specific weaning protocol in an intensive care unit setting: a retrospective study

OBJECTIVES: A number of complications exist with invasive mechanical ventilation and with the use of and withdrawal from prolonged ventilator support. The use of protocols that enable the systematic identification of patients eligible for an interruption in mechanical ventilation can significantly reduce the number of complications. This study describes the application of a weaning protocol and its results. METHODS: Patients who required invasive mechanical ventilation for more than 24 hours were included and assessed daily to identify individuals who were ready to begin the weaning process. RESULTS: We studied 252 patients with a median mechanical ventilation time of 3.7 days (interquartile range of 1 to 23 days), a rapid shallow breathing index value of 48 (median), a maximum inspiratory pressure of 40 cmH2O, and a maximum expiratory pressure of 40 cm H2O (median). Of these 252 patients, 32 (12.7%) had to be reintubated, which represented weaning failure. Noninvasive ventilation was used postextubation in 170 (73%) patients, and 15% of these patients were reintubated, which also represented weaning failure. The mortality rate of the 252 patients studied was 8.73% (22), and there was no significant difference in the age, gender, mechanical ventilation time, and maximum inspiratory pressure between the survivors and nonsurvivors. CONCLUSIONS: The use of a specific weaning protocol resulted in a lower mechanical ventilation time and an acceptable reintubation rate. This protocol can be used as a comparative index in hospitals to improve the weaning system, its monitoring and the informative reporting of patient outcomes and may represent a future tool and source of quality markers for patient care.

Comparison of 3 modes of automated weaning from mechanical ventilation: A bench study

Purpose: Automated weaning modes are available in some mechanical ventilators, but no studies compared them hitherto. We compared the performance of 3 automated modes under standard and challenging situations. Methods: We used a lung simulator to compare 3 automated modes, adaptive support ventilation (ASV), mandatory rate ventilation (MRV), and Smartcare, in 6 situations, weaning success, weaning failure, weaning success with extreme anxiety, weaning success with Cheyne-Stokes, weaning success with irregular breathing, and weaning failure with ineffective efforts. Results: The 3 modes correctly recognized the situations of weaning success and failure, even when anxiety or irregular breathing were present but incorrectly recognized weaning success with Cheyne-Stokes. MRV incorrectly recognized weaning failure with ineffective efforts. Time to pressure support (PS) stabilization was shorter for ASV (1-2 minutes for all situations) and MRV (1-7 minutes) than for Smartcare (8-78 minutes). ASV had higher rates of PS oscillations per 5 minutes (4-15), compared with Smartcare (0-1) and MRV (0-12), except when extreme anxiety was present. Conclusions: Smartcare, ASV, and MRV were equally able to recognize weaning success and failure, despite the presence of anxiety or irregular breathing but performed incorrectly in the presence of Cheyne-Stokes. PS behavior over the time differs among modes, with ASV showing larger and more frequent PS oscillations over the time. Clinical studies are needed to confirm our results. (C) 2012 Elsevier Inc. All rights reserved.

Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome A Meta-analysis

Context Lung-protective mechanical ventilation with the use of lower tidal volumes has been found to improve outcomes of patients with acute respiratory distress syndrome (ARDS). It has been suggested that use of lower tidal volumes also benefits patients who do not have ARDS. Objective To determine whether use of lower tidal volumes is associated with improved outcomes of patients receiving ventilation who do not have ARDS. Data Sources MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials up to August 2012. Study Selection Eligible studies evaluated use of lower vs higher tidal volumes in patients without ARDS at onset of mechanical ventilation and reported lung injury development, overall mortality, pulmonary infection, atelectasis, and biochemical alterations. Data Extraction Three reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. Data Synthesis Twenty articles (2822 participants) were included. Meta-analysis using a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33; 95% CI, 0.23 to 0.47; I-2, 0%; number needed to treat [NNT], 11), and mortality (RR, 0.64; 95% CI, 0.46 to 0.89; I-2, 0%; NNT, 23) in patients receiving ventilation with lower tidal volumes. The results of lung injury development were similar when stratified by the type of study (randomized vs nonrandomized) and were significant only in randomized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-analysis using a random-effects model showed, in protective ventilation groups, a lower incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I-2, 32%; NNT, 26), lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively; standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I-2, 75%), higher mean (SD) PaCO2 levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, -0.51; 95% CI, -0.70 to -0.32; I-2, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04], respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I-2, 96%) but similar mean (SD) ratios of PaO2 to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD, 0.11; 95% CI, -0.06 to 0.27; I-2, 60%). Tidal volume gradients between the 2 groups did not influence significantly the final results. Conclusions Among patients without ARDS, protective ventilation with lower tidal volumes was associated with better clinical outcomes. Some of the limitations of the meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or operating room) and the duration of mechanical ventilation. JAMA. 2012;308(16):1651-1659 www.jama.com

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.

Goal-directed fluid management based on pulse pressure variation monitoring during high-risk surgery: a pilot randomized controlled trial

Abstract Introduction Several studies have shown that maximizing stroke volume (or increasing it until a plateau is reached) by volume loading during high-risk surgery may improve post-operative outcome. This goal could be achieved simply by minimizing the variation in arterial pulse pressure (ΔPP) induced by mechanical ventilation. We tested this hypothesis in a prospective, randomized, single-centre study. The primary endpoint was the length of postoperative stay in hospital. Methods Thirty-three patients undergoing high-risk surgery were randomized either to a control group (group C, n = 16) or to an intervention group (group I, n = 17). In group I, ΔPP was continuously monitored during surgery by a multiparameter bedside monitor and minimized to 10% or less by volume loading. Results Both groups were comparable in terms of demographic data, American Society of Anesthesiology score, type, and duration of surgery. During surgery, group I received more fluid than group C (4,618 ± 1,557 versus 1,694 ± 705 ml (mean ± SD), P < 0.0001), and ΔPP decreased from 22 ± 75 to 9 ± 1% (P < 0.05) in group I. The median duration of postoperative stay in hospital (7 versus 17 days, P < 0.01) was lower in group I than in group C. The number of postoperative complications per patient (1.4 ± 2.1 versus 3.9 ± 2.8, P < 0.05), as well as the median duration of mechanical ventilation (1 versus 5 days, P < 0.05) and stay in the intensive care unit (3 versus 9 days, P < 0.01) was also lower in group I. Conclusion Monitoring and minimizing ΔPP by volume loading during high-risk surgery improves postoperative outcome and decreases the length of stay in hospital. Trial registration NCT00479011

Endotracheal suction in intubated critically ill adult patients undergoing mechanical ventilation: a systematic review

AIM: identify and analyze in the literature the evidence of randomized controlled trials on care related to the suctioning of endotracheal secretions in intubated, critically ill adult patients undergoing mechanical ventilation. METHOD: the search was conducted in the PubMed, EMBASE, CENTRAL, CINAHL and LILACS databases. From the 631 citations found, 17 studies were selected. RESULTS: Evidence was identified for six categories of intervention related to endotracheal suctioning, which were analyzed according to outcomes related to hemodynamic and blood gas alterations, microbial colonization, nosocomial infection, and others. CONCLUSIONS: although the evidence obtained is relevant to the practice of endotracheal aspiration, the risks of bias found in the studies selected compromise the evidence's reliability.

Performance of supraglottic airway devices and 12 month skill retention: a randomized controlled study with manikins

Airway management for successful ventilation by laypersons and inexperienced healthcare providers is difficult to achieve. Bag-valve mask (BVM) ventilation requires extensive training and is performed poorly. Supraglottic airway devices (SADs) have been successfully introduced to clinical resuscitation practice as an alternative. We evaluated recently introduced (i-gel™ and LMA-Supreme™) and established SADs (LMA-Unique™, LMA-ProSeal™) and BVM used by laypeople in training sessions on manikins.

Influence of end-expiratory level and tidal volume on gravitational ventilation distribution during tidal breathing in healthy adults

Our understanding of regional filling of the lung and regional ventilation distribution is based on studies using stepwise inhalation of radiolabelled tracer gases, magnetic resonance imaging and positron emission tomography. We aimed to investigate whether these differences in ventilation distribution at different end-expiratory levels (EELs) and tidal volumes (V (T)s) held also true during tidal breathing. Electrical impedance tomography (EIT) measurements were performed in ten healthy adults in the right lateral position. Five different EELs with four different V (T)s at each EEL were tested in random order, resulting in 19 combinations. There were no measurements for the combination of the highest EEL/highest V (T). EEL and V (T) were controlled by visual feedback based on airflow. The fraction of ventilation directed to different slices of the lung (VENT(RL1)-VENT(RL8)) and the rate of the regional filling of each slice versus the total lung were analysed. With increasing EEL but normal tidal volume, ventilation was preferentially distributed to the dependent lung and the filling of the right and left lung was more homogeneous. With increasing V (T) and maintained normal EEL (FRC), ventilation was preferentially distributed to the dependent lung and regional filling became more inhomogeneous (p < 0.05). We could demonstrate that regional and temporal ventilation distribution during tidal breathing was highly influenced by EEL and V (T).

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection: a meta-analysis of randomised controlled trials

BACKGROUND: The objective of this study was to review the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with Pneumocystis jiroveci pneumonia (PCP) and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air). METHODS: We conducted a systematic search of the literature for randomised trials published up to December 2004. Selected trials compared adjunctive corticosteroids with placebo or usual care in HIV-infected patients with PCP and reported mortality data. Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. RESULTS: Six studies were included in the meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.54 (95% confidence interval [CI], 0.38-0.79) at 1 month and 0.67 (95% CI, 0.49-0.93) at 3-4 months of follow-up. Numbers needed to treat, to prevent 1 death, are 9 patients in a setting without highly active antiretroviral therapy (HAART) available and 22 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.37 (95% CI, 0.20-0.70) in favour of adjunctive corticosteroids. CONCLUSION: The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but our results suggest a beneficial effect for patients with substantial hypoxemia.

Population pharmacokinetics of sevoflurane in conjunction with the AnaConDa: toward target-controlled infusion of volatiles into the breathing system

BACKGROUND: The Anesthetic Conserving Device (AnaConDa) uncouples delivery of a volatile anesthetic (VA) from fresh gas flow (FGF) using a continuous infusion of liquid volatile into a modified heat-moisture exchanger capable of adsorbing VA during expiration and releasing adsorbed VA during inspiration. It combines the simplicity and responsiveness of high FGF with low agent expenditures. We performed in vitro characterization of the device before developing a population pharmacokinetic model for sevoflurane administration with the AnaConDa, and retrospectively testing its performance (internal validation). MATERIALS AND METHODS: Eighteen females and 20 males, aged 31-87, BMI 20-38, were included. The end-tidal concentrations were varied and recorded together with the VA infusion rates into the device, ventilation and demographic data. The concentration-time course of sevoflurane was described using linear differential equations, and the most suitable structural model and typical parameter values were identified. The individual pharmacokinetic parameters were obtained and tested for covariate relationships. Prediction errors were calculated. RESULTS: In vitro studies assessed the contribution of the device to the pharmacokinetic model. In vivo, the sevoflurane concentration-time courses on the patient side of the AnaConDa were adequately described with a two-compartment model. The population median absolute prediction error was 27% (interquartile range 13-45%). CONCLUSION: The predictive performance of the two-compartment model was similar to that of models accepted for TCI administration of intravenous anesthetics, supporting open-loop administration of sevoflurane with the AnaConDa. Further studies will focus on prospective testing and external validation of the model implemented in a target-controlled infusion device.

Pain relief in ventilated preterms during endotracheal suctioning: a randomized controlled trial

BACKGROUND: In Switzerland approximately 8% of infants are born prematurely. Some of them undergo mechanical ventilation including endotracheal suctioning (ETS). ETS is one of the most frequently performed interventions and is linked to stress and pain, but its treatment is controversial. In Switzerland there is a lack of standardisation in pain relief for ETS. AIMS: To test the hypothesis that an intermittent dose of morphine reduces pain during ETS and that subsequent multisensorial stimulation (MSS), as a non pharmacological comforting intervention, helps infants to recover from experienced pain. METHOD: A randomized placebo controlled trial in two tertiary neonatal intensive care units (NICU) with a sample of 30 mechanically ventilated preterm infants was conducted. Pain was measured by three pain assessment tools (Bernese Pain Scale for Neonates, Premature Infant Pain Profile and Visual Analogue Scale) RESULTS: Morphine did not lead to any pain relief from ETS as measured by three pain scales. Nor did the comforting intervention of MSS show any effect. Repeated-measure analysis of variance for the within and between groups comparison showed no statistical significance. CONCLUSIONS: The administration of morphine for pain relief in ventilated preterm neonates during ETS remains questionable and the use of MSS as a comforting intervention after painful stimulus cannot be recommended. The validity testing of the instruments for this patient population should undergo a systematic validation trajectory. Future research should focus on options among non pharmacological interventions for relieving pain during ETS.

Blind intubation of anaesthetised children with supraglottic airway devices AmbuAura-i and Air-Q cannot be recommended: A randomised controlled trial.

BACKGROUND Paediatric supraglottic airway devices AmbuAura-i and Air-Q were designed as conduits for tracheal intubation. Although fibreoptic-guided intubation has proved successful, blind intubation as a rescue technique has never been evaluated. OBJECTIVE Evaluation of blind intubation through AmbuAura-i and Air-Q. On the basis of fibreoptic view data, we hypothesised that the success rate with the AmbuAura-i would be higher than with the Air-Q. DESIGN A prospective, randomised controlled trial with institutional review board (IRB) approval and written informed consent. SETTING University Childrens' Hospital; September 2012 to July 2014. PATIENTS Eighty children, American Society of Anesthesiologists (ASA) class I to III, weight 5 to 50 kg. INTERVENTIONS Tracheal intubation was performed through the randomised device with the tip of a fibrescope placed inside and proximal to the tip of the tracheal tube. This permitted sight of tube advancement, but without fibreoptic guidance (visualised blind intubation). MAIN OUTCOME MEASURES Primary outcome was successfully visualised blind intubation; secondary outcomes included supraglottic airway device success, insertion times, airway leak pressure, fibreoptic view and adverse events. RESULTS Personal data did not differ between groups. In contrast to our hypothesis, blind intubation was possible in 15% with the Air-Q and in 3% with the AmbuAura-i [95% confidence interval (95% CI) 6 to 31 vs. 0 to 13%; P = 0.057]. First attempt supraglottic airway device insertion success rates were 95% (Air-Q) and 100% (AmbuAura-i; 95% CI 83 to 99 vs. 91 to 100; P = 0.49). Median leak pressures were 18 cmH2O (Air-Q) and 17 cmH2O [AmbuAura-i; interquartile range (IQR) 14 to 18 vs. 14 to 19 cmH2O; P = 0.66]. Air-Q insertion was slower (27 vs. 19 s, P < 0.001). There was no difference in fibreoptic view, or adverse events (P > 0.05). In one child (Air-Q size 1.5, tube size 3.5), the tube dislocated during device removal. CONCLUSION Ventilation with both devices is reliable, but success of blind intubation is unacceptably low and cannot be recommended for elective or rescue purposes. If intubation through a paediatric supraglottic airway device is desired, we suggest that fibreoptic guidance is used. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01692522.

Hypotensive resuscitation versus standard fluid resuscitation for the management of trauma patients in hemorrhagic shock: The safety phase of a randomized controlled trial

Trauma is a leading cause of death worldwide, and is thus a major public health concern. Improving current resuscitation strategies may help to reduce morbidity and mortality from trauma, and clinical research plays an important role in addressing these issues. This thesis is a secondary analysis of data that was collected for a randomized clinical trial being conducted at Ben Taub General Hospital. The trial is designed to compare a hypotensive resuscitation strategy to standard fluid resuscitation for the early treatment of trauma patients in hemorrhagic shock. This thesis examines the clinical outcomes from the first 90 subjects enrolled in the study, with the primary aim of assessing the safety of hypotensive resuscitation within the trauma population. ^ Patients in hemorrhagic shock who required emergent surgery were randomized to one of two arms of the study. Those in the experimental (LMAP) arm were managed with a hypotensive resuscitation strategy in which the target mean arterial pressure was 50mmHg. Those in the control (HMAP) arm were managed with standard fluid resuscitation to a target mean arterial pressure of 65mmHg. Patients were followed for 30 days. Mortality, post-operative complications, and other clinical data were prospectively gathered by the Ben Taub surgical staff and then secondarily analyzed for the purpose of this thesis.^ Subjects in the LMAP group had significantly lower early post-operative mortality compared to those in the HMAP group. 30-day mortality was also lower in the LMAP group, although this did not reach statistical significance. There were no statistically significant differences between the two groups with regards to development of ischemic, hematologic or infectious complications, length of hospitalization, length of ICU stay or duration of mechanical ventilation. ^ Based upon the data presented in this thesis, it appears that hypotensive resuscitation is a safe strategy for use in the trauma population. Specifically, hypotensive resuscitation reduced the risk of early post-operative death from coagulopathic bleeding and did not result in an increased risk of ischemic or other post-operative complications. The preliminary results described in this thesis provide convincing evidence support the continued investigation and use of hypotensive resuscitation in a trauma setting.^