The Modified Apnea Test During Brain Death Determination: An Alternative in Patients With Hypoxia.

INTRODUCTION: Conventional apnea testing in patients with severe hypoxemia or hemodynamic instability with removal from the ventilator support is unsafe. We describe an alternative approach to apnea testing, which may be used in patients with hypoxia unable to undergo conventional apnea testing. METHODS: Case Report. A 42-year-old man had a severe traumatic brain injury resulting in diffuse cerebral edema and subarachnoid hemorrhage with herniation. His presentation was complicated by hypoxic respiratory failure from pulmonary contusions and hemorrhagic shock. On hospital day 2, the patient lost brain stem reflexes. Brain death testing with conventional apnea testing was attempted but aborted due to hypoxia. RESULTS: A modified apnea test was applied, which had been approved by appropriate hospital committees including critical care operations, ethics, and the brain death protocol council. Minute ventilation was gradually decreased by ≥50% to attain a PaCo2 level ≥20 mm Hg above baseline. The ventilation mode was then switched from volume control to continuous positive airway pressure while observing the patient for signs of respiration for a duration of 60 seconds. CONCLUSION: The modified apnea test does not require circuit disconnection and can be successfully applied to determine brain death without compromising safety in high-risk patients having severe hypoxia.

T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial.

BACKGROUND: Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2-5 days to grow. We present the results of the first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia. METHODS: Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from <1 to 100 colony-forming units (CFUs)/mL for 5 different Candida species. RESULTS: T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%-99.6%) with a mean time to negative result of 4.2 ± 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 ± 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively. CONCLUSIONS: T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics. CLINICAL TRIALS REGISTRATION: NCT01752166.

Hand hygiene knowledge and perceptions among anesthesia providers.

BACKGROUND: Health care worker compliance with hand hygiene guidelines is an important measure for health care-associated infection prevention, yet overall compliance across all health care arenas remains low. A correct answer to 4 of 4 structured questions pertaining to indications for hand decontamination (according to types of contact) has been associated with improved health care provider hand hygiene compliance when compared to those health care providers answering incorrectly for 1 or more questions. A better understanding of knowledge deficits among anesthesia providers may lead to hand hygiene improvement strategies. In this study, our primary aims were to characterize and identify predictors for hand hygiene knowledge deficits among anesthesia providers. METHODS: We modified this previously tested survey instrument to measure anesthesia provider hand hygiene knowledge regarding the 5 moments of hand hygiene across national and multicenter groups. Complete knowledge was defined by correct answers to 5 questions addressing the 5 moments for hand hygiene and received a score of 1. Incomplete knowledge was defined by an incorrect answer to 1 or more of the 5 questions and received a score of 0. We used a multilevel random-effects XTMELOGIT logistic model clustering at the respondent and geographic location for insufficient knowledge and forward/backward stepwise logistic regression analysis to identify predictors for incomplete knowledge. RESULTS: The survey response rates were 55.8% and 18.2% for the multicenter and national survey study groups, respectively. One or more knowledge deficits occurred with 81.6% of survey respondents, with the mean number of correct answers 2.89 (95% confidence interval, 2.78- 2.99). Failure of providers to recognize prior contact with the environment and prior contact with the patient as hand hygiene opportunities contributed to the low mean. Several cognitive factors were associated with a reduced risk of incomplete knowledge including providers responding positively to washing their hands after contact with the environment (odds ratio [OR] 0.23, 0.14-0.37, P < 0.001), disinfecting their environment during patient care (OR 0.54, 0.35-0.82, P = 0.004), believing that they can influence their colleagues (OR 0.43, 0.27-0.68, P < 0.001), and intending to adhere to guidelines (OR 0.56, 0.36-0.86, P = 0.008). These covariates were associated with an area under receiver operator characteristics curve of 0.79 (95% confidence interval, 0.74-0.83). CONCLUSIONS: Anesthesia provider knowledge deficits around to hand hygiene guidelines occur frequently and are often due to failure to recognize opportunities for hand hygiene after prior contact with contaminated patient and environmental reservoirs. Intraoperative hand hygiene improvement programs should address these knowledge deficits. Predictors for incomplete knowledge as identified in this study should be validated in future studies.

Transmission dynamics of gram-negative bacterial pathogens in the anesthesia work area.

BACKGROUND: Gram-negative organisms are a major health care concern with increasing prevalence of infection and community spread. Our primary aim was to characterize the transmission dynamics of frequently encountered gram-negative bacteria in the anesthesia work area environment (AWE). Our secondary aim was to examine links between these transmission events and 30-day postoperative health care-associated infections (HCAIs). METHODS: Gram-negative isolates obtained from the AWE (patient nasopharynx and axilla, anesthesia provider hands, and the adjustable pressure-limiting valve and agent dial of the anesthesia machine) at 3 major academic medical centers were identified as possible intraoperative bacterial transmission events by class of pathogen, temporal association, and phenotypic analysis (analytical profile indexing). The top 5 frequently encountered genera were subjected to antibiotic disk diffusion sensitivity to identify epidemiologically related transmission events. Complete multivariable logistic regression analysis and binomial tests of proportion were then used to examine the relative contributions of reservoirs of origin and within- and between-case modes of transmission, respectively, to epidemiologically related transmission events. Analyses were conducted with and without the inclusion of duplicate transmission events of the same genera occurring in a given study unit (first and second case of the day in each operating room observed) to examine the potential effect of statistical dependency. Transmitted isolates were compared by pulsed-field gel electrophoresis to disease-causing bacteria for 30-day postoperative HCAIs. RESULTS: The top 5 frequently encountered gram-negative genera included Acinetobacter, Pseudomonas, Brevundimonas, Enterobacter, and Moraxella that together accounted for 81% (767/945) of possible transmission events. For all isolates, 22% (167/767) of possible transmission events were identified by antibiotic susceptibility patterns as epidemiologically related and underwent further study of transmission dynamics. There were 20 duplicates involving within- and between-case transmission events. Thus, approximately 19% (147/767) of isolates excluding duplicates were considered epidemiologically related. Contaminated provider hand reservoirs were less likely (all isolates, odds ratio 0.12, 95% confidence interval 0.03-0.50, P = 0.004; without duplicate events, odds ratio 0.05, 95% confidence interval 0.01-0.49, P = 0.010) than contaminated patient or environmental sites to serve as the reservoir of origin for epidemiologically related transmission events. Within- and between-case modes of gram-negative bacilli transmission occurred at similar rates (all isolates, 7% between-case, 5.2% within-case, binomial P value 0.176; without duplicates, 6.3% between-case, 3.7% within-case, binomial P value 0.036). Overall, 4.0% (23/548) of patients suffered from HCAIs and had an intraoperative exposure to gram-negative isolates. In 8.0% (2/23) of those patients, gram-negative bacteria were linked by pulsed-field gel electrophoresis to the causative organism of infection. Patient and provider hands were identified as the reservoirs of origin and the environment confirmed as a vehicle for between-case transmission events linked to HCAIs. CONCLUSIONS: Between- and within-case AWE gram-negative bacterial transmission occurs frequently and is linked by pulsed-field gel electrophoresis to 30-day postoperative infections. Provider hands are less likely than contaminated environmental or patient skin surfaces to serve as the reservoir of origin for transmission events.

The epidemiology of Staphylococcus aureus transmission in the anesthesia work area.

BACKGROUND: Little is known regarding the epidemiology of intraoperative Staphylococcus aureus transmission. The primary aim of this study was to examine the mode of transmission, reservoir of origin, transmission locations, and antibiotic susceptibility for frequently encountered S aureus strains (phenotypes) in the anesthesia work area. Our secondary aims were to examine phenotypic associations with 30-day postoperative patient cultures, phenotypic growth rates, and risk factors for phenotypic isolation. METHODS: S aureus isolates previously identified as possible intraoperative bacterial transmission events by class of pathogen, temporal association, and analytical profile indexing were subjected to antibiotic disk diffusion sensitivity. The combination of these techniques was then used to confirm S aureus transmission events and to classify them as occurring within or between operative cases (mode). The origin of S aureus transmission events was determined via use of a previously validated experimental model and links to 30-day postoperative patient cultures confirmed via pulsed-field gel electrophoresis. Growth rates were assessed via time-to-positivity analysis, and risk factors for isolation were characterized via logistic regression. RESULTS: One hundred seventy S aureus isolates previously implicated as possible intraoperative transmission events were further subdivided by analytical profile indexing phenotype. Two phenotypes, phenotype P (patients) and phenotype H (hands), accounted for 65% of isolates. Phenotype P and phenotype H contributed to at least 1 confirmed transmission event in 39% and 28% of cases, respectively. Patient skin surfaces (odds ratio [OR], 8.40; 95% confidence interval [CI], 2.30-30.73) and environmental (OR, 10.89; 95% CI, 1.29-92.13) samples were more likely than provider hands (referent) to have phenotype P positivity. Phenotype P was more likely than phenotype H to be resistant to methicillin (OR, 4.38; 95% CI, 1.59-12.06; P = 0.004) and to be linked to 30-day postoperative patient cultures (risk ratio, 36.63 [risk difference, 0.174; 95% CI, 0.019-0.328]; P < 0.001). Phenotype P exhibited a faster growth rate for methicillin resistant and for methicillin susceptible than phenotype H (phenotype P: median, 10.32H; interquartile range, 10.08-10.56; phenotype H: median, 10.56H; interquartile range, 10.32-10.8; P = 0.012). Risk factors for isolation of phenotype P included age (OR, 14.11; 95% CI, 3.12-63.5; P = 0.001) and patient exposure to the hospital ward (OR, 41.11; 95% CI, 5.30-318.78; P < 0.001). CONCLUSIONS: Two S aureus phenotypes are frequently transmitted in the anesthesia work area. A patient and environmentally derived phenotype is associated with increased risk of antibiotic resistance and links to 30-day postoperative patient cultures as compared with a provider hand-derived phenotype. Future work should be directed toward improved screening and decolonization of patients entering the perioperative arena and improved intraoperative environmental cleaning to attenuate postoperative health care-associated infections.

The dynamics of Enterococcus transmission from bacterial reservoirs commonly encountered by anesthesia providers.

BACKGROUND: Enterococci, the second leading cause of health care-associated infections, have evolved from commensal and harmless organisms to multidrug-resistant bacteria associated with a significant increase in patient morbidity and mortality. Prevention of ongoing spread of this organism within and between hospitals is important. In this study, we characterized Enterococcus transmission dynamics for bacterial reservoirs commonly encountered by anesthesia providers during the routine administration of general anesthesia. METHODS: Enterococcus isolates previously obtained from bacterial reservoirs frequently encountered by anesthesiologists (patient nasopharynx and axilla, anesthesia provider hands, and the adjustable pressure-limiting valve and agent dial of the anesthesia machine) at 3 major academic medical centers were identified as possible intraoperative bacterial transmission events by class of pathogen, temporal association, and phenotypic analysis (analytical profile indexing). They were then subjected to antibiotic disk diffusion sensitivity for transmission event confirmation. Isolates involved in confirmed transmission events were further analyzed to characterize the frequency, mode, origin, location of transmission events, and antibiotic susceptibility of transmitted pathogens. RESULTS: Three hundred eighty-nine anesthesia reservoir isolates were previously identified by gross morphology and simple rapid tests as Enterococcus. The combination of further analytical profile indexing analysis and temporal association implicated 43% (166/389) of those isolates in possible intraoperative bacterial transmission events. Approximately, 30% (49/166) of possible transmission events were confirmed by additional antibiotic disk diffusion analysis. Two phenotypes, E5 and E7, explained 80% (39/49) of confirmed transmission events. For both phenotypes, provider hands were a common reservoir of origin proximal to the transmission event (96% [72/75] hand origin for E7 and 89% [50/56] hand origin for E5) and site of transmission (94% [16/17] hand transmission location for E7 and 86% [19/22] hand transmission location for E5). CONCLUSIONS: Anesthesia provider hand contamination is a common proximal source and transmission location for Enterococcus transmission events in the anesthesia work area. Future work should evaluate the impact of intraoperative hand hygiene improvement strategies on the dynamics of intraoperative Enterococcus transmission.

The bundle "plus": the effect of a multidisciplinary team approach to eradicate central line-associated bloodstream infections.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) have decreased significantly over the last decade. Further reductions in CLABSI rates should be possible. We describe a multidisciplinary approach to the reduction of CLABSIs. METHODS: This was an observational study of critically ill patients requiring central venous catheters in 8 intensive care units in a tertiary medical center. We implemented a catheter bundle that included hand hygiene, education of providers, chlorhexidine skin preparation, use of maximum barrier precautions, a dedicated line cart, checklist, avoidance of the femoral vein for catheter insertion, chlorhexidine-impregnated dressings, use of anti-infective catheters, and daily consideration of the need for the catheter. Additional measures included root cause analyses of all CLABSIs, creation of a best practice atlas for internal jugular catheters, and enhanced education on blood culture collection. Data were analyzed using the Poisson test and regression. RESULTS: CLABSI, catheter use, and microbiology were tracked from 2004 to 2012. There was a 92% reduction in CLABSIs (95% lower confidence limit: 67.4% reduction, P < 0.0001). Central venous catheter use decreased significantly from 2008 to 2012 (P = 0.032, -151 catheters per year, 95% confidence limits: -277 to -25), whereas peripherally inserted central catheter use increased (P = 0.005, 89 catheters per year, 95% confidence limits: 50 to 127). There was no apparent association between unit-specific Acute Physiology And Chronic Health Evaluation III/IV scores and CLABSI. Three units have not had a CLABSI in more than a year. The most common organism isolated was coagulase-negative staphylococcus. Since the implementation of minocycline/rifampin catheters, no cases of methicillin-resistant Staphylococcus aureus CLABSI have occurred. CONCLUSIONS: The implementation of a standard catheter bundle combined with chlorhexidine dressings, minocycline/rifampin catheters, and other behavioral changes was associated with a sustained reduction in CLABSIs.

An evaluation of the diagnostic accuracy of the 1991 American College of Chest Physicians/Society of Critical Care Medicine and the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine/American College of Chest Physicians/American Thoracic Society/Surgical Infection Society sepsis definition.

OBJECTIVES: Limited research has been conducted to compare the test characteristics of the 1991 and 2001 sepsis consensus definitions. This study assessed the accuracy of the two sepsis consensus definitions among adult critically ill patients compared to sepsis case adjudication by three senior clinicians. DESIGN: Observational study of patients admitted to intensive care units. SETTING: Seven intensive care units of an academic medical center. PATIENTS: A random sample of 960 patients from all adult intensive care unit patients between October 2007 and December 2008. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sensitivity, specificity, and the area under the receiver operating characteristic curve for the two consensus definitions were calculated by comparing the number of patients who met or did not meet consensus definitions vs. the number of patients who were or were not diagnosed with sepsis by adjudication. The 1991 sepsis definition had a high sensitivity of 94.6%, but a low specificity of 61.0%. The 2001 sepsis definition had a slightly increased sensitivity but a decreased specificity, which were 96.9% and 58.3%, respectively. The areas under the receiver operating characteristic curve for the two definitions were not statistically different (0.778 and 0.776, respectively). The sensitivities and areas under the receiver operating characteristic curve of both definitions were lower at the 24-hr time window level than those of the intensive care unit stay level, though their specificities increased slightly. Fever, high white blood cell count or immature forms, low Glasgow coma score, edema, positive fluid balance, high cardiac index, low PaO2/FIO2 ratio, and high levels of creatinine and lactate were significantly associated with sepsis by both definitions and adjudication. CONCLUSIONS: Both the 1991 and the 2001 sepsis definition have a high sensitivity but low specificity; the 2001 definition has a slightly increased sensitivity but a decreased specificity compared to the 1991 definition. The diagnostic performances of both definitions were suboptimal. A parsimonious set of significant predictors for sepsis diagnosis is likely to improve current sepsis case definitions.

Multiple reservoirs contribute to intraoperative bacterial transmission.

BACKGROUND: Intraoperative stopcock contamination is a frequent event associated with increased patient mortality. In the current study we examined the relative contributions of anesthesia provider hands, the patient, and the patient environment to stopcock contamination. Our secondary aims were to identify risk factors for stopcock contamination and to examine the prior association of stopcock contamination with 30-day postoperative infection and mortality. Additional microbiological analyses were completed to determine the prevalence of bacterial pathogens within intraoperative bacterial reservoirs. Pulsed-field gel electrophoresis was used to assess the contribution of reservoir bacterial pathogens to 30-day postoperative infections. METHODS: In a multicenter study, stopcock transmission events were observed in 274 operating rooms, with the first and second cases of the day in each operating room studied in series to identify within- and between-case transmission events. Reservoir bacterial cultures were obtained and compared with stopcock set isolates to determine the origin of stopcock contamination. Between-case transmission was defined by the isolation of 1 or more bacterial isolates from the stopcock set of a subsequent case (case 2) that were identical to reservoir isolates from the preceding case (case 1). Within-case transmission was defined by the isolation of 1 or more bacterial isolates from a stopcock set that were identical to bacterial reservoirs from the same case. Bacterial pathogens within these reservoirs were identified, and their potential contribution to postoperative infections was evaluated. All patients were followed for 30 days postoperatively for the development of infection and all-cause mortality. RESULTS: Stopcock contamination was detected in 23% (126 out of 548) of cases with 14 between-case and 30 within-case transmission events confirmed. All 3 reservoirs contributed to between-case (64% environment, 14% patient, and 21% provider) and within-case (47% environment, 23% patient, and 30% provider) stopcock transmission. The environment was a more likely source of stopcock contamination than provider hands (relative risk [RR] 1.91, confidence interval [CI] 1.09 to 3.35, P = 0.029) or patients (RR 2.56, CI 1.34 to 4.89, P = 0.002). Hospital site (odds ratio [OR] 5.09, CI 2.02 to 12.86, P = 0.001) and case 2 (OR 6.82, CI 4.03 to 11.5, P < 0.001) were significant predictors of stopcock contamination. Stopcock contamination was associated with increased mortality (OR 58.5, CI 2.32 to 1477, P = 0.014). Intraoperative bacterial contamination of patients and provider hands was linked to 30-day postoperative infections. CONCLUSIONS: Bacterial contamination of patients, provider hands, and the environment contributes to stopcock transmission events, but the surrounding patient environment is the most likely source. Stopcock contamination is associated with increased patient mortality. Patient and provider bacterial reservoirs contribute to 30-day postoperative infections. Multimodal programs designed to target each of these reservoirs in parallel should be studied intensely as a comprehensive approach to reducing intraoperative bacterial transmission.

Anti-infective external coating of central venous catheters: a randomized, noninferiority trial comparing 5-fluorouracil with chlorhexidine/silver sulfadiazine in preventing catheter colonization.

OBJECTIVE: The antimetabolite drug, 5-fluorouracil, inhibits microbial growth. Coating of central venous catheters with 5-fluorouracil may reduce the risk of catheter infection. Our objective was to compare the safety and efficacy of central venous catheters externally coated with 5-fluorouracil with those coated with chlorhexidine and silver sulfadiazine. DESIGN: Prospective, single-blind, randomized, active-controlled, multicentered, noninferiority trial. SETTING: Twenty-five US medical center intensive care units. PATIENTS: A total of 960 adult patients requiring central venous catheterization for up to 28 days. INTERVENTIONS: Patients were randomized to receive a central venous catheter externally coated with either 5-fluorouracil (n = 480) or chlorhexidine and silver sulfadiazine (n = 480). MEASUREMENTS AND MAIN RESULTS: The primary antimicrobial outcome was a dichotomous measure (<15 colony-forming units or ≥ 15 colony-forming units) for catheter colonization determined by the roll plate method. Secondary antimicrobial outcomes included local site infection and catheter-related bloodstream infection. Central venous catheters coated with 5-fluorouracil were noninferior to chlorhexidine and silver sulfadiazine coated central venous catheters with respect to the incidence of catheter colonization (2.9% vs. 5.3%, respectively). Local site infection occurred in 1.4% of the 5-fluorouracil group and 0.9% of the chlorhexidine and silver sulfadiazine group. No episode of catheter-related bloodstream infection occurred in the 5-fluorouracil group, whereas two episodes were noted in the chlorhexidine and silver sulfadiazine group. Only Gram-positive organisms were cultured from 5-fluorouracil catheters, whereas Gram-positive bacteria, Gram-negative bacteria, and Candida were cultured from the chlorhexidine and silver sulfadiazine central venous catheters. Adverse events were comparable between the two central venous catheter coatings. CONCLUSIONS: Our results suggest that central venous catheters externally coated with 5-fluorouracil are a safe and effective alternative to catheters externally coated with chlorhexidine and silver sulfadiazine when used in critically ill patients.

Pancreatitis associated with Strongyloides stercoralis infection in a patient chronically treated with corticosteroids.

Strongyloides stercoralis is a nematode that is a ubiquitous parasite in man. Life-threatening infections can occur in immunocompromised patients. We report a case of a 64-year-old Puerto Rican gentleman treated chronically with corticosteroids for reactive airway disease, who presented to our institution with pancreatitis complicated by sepsis and acute lung injury requiring mechanical ventilation. The initial working diagnosis was gallstone pancreatitis; however, several days into his hospital course, he was found to have a history of strongyloidiasis. Subsequent examination of his stool revealed the parasite, and the patient was treated with ivermectin. This case highlights the occasional association between pancreatitis and strongyloidiasis and the importance of proper treatment and consideration of infection in patients from endemic regions, which include Central America, Africa, and Asia.

Prevention of central venous catheter bloodstream infections.

The majority of nosocomial bloodstream infections in critically ill patients originate from an infected central venous catheter (CVC). Catheter-related bloodstream infections (CRBSIs) cause significant morbidity and mortality and increase the cost of care. The most frequent causative organisms for CRBSI are coagulase-negative staphylococci (CoNSs), Staphylococcus aureus, enterococci, and Candida species. The path to infection frequently includes migration of skin organisms at the insertion site into the cutaneous catheter tract, resulting in microbial colonization of the catheter tip and formation of biofilm. Evidence-based strategies for the prevention of CRBSI include behavioral and educational interventions, effective skin antisepsis coupled with maximum barrier precautions, the use of antiseptic dressings, and the use of antiseptic or antibiotic impregnated catheters. Achieving and maintaining very low rates of CRBSI requires a multidisciplinary approach involving the entire health care team, the use of novel technologies in patients with the highest risk of CRBSI, and frequent reeducation of staff.

Airway Management in Critical Illness: An Update.

Expertise in airway management is a vital skill for any provider caring for critically ill patients. A growing body of literature has identified the stark difference in periprocedural outcomes of elective intubation in the operating room when compared with emergency intubation in the ICU. A number of strategies to reduce the morbidity and mortality associated with airway management in the critically ill have been described. In this review, we provide an updated framework for airway assessment before direct laryngoscopy and video laryngoscopy, and use of newer pharmacologic agents; comment on current concepts in tracheal intubation in the ICU; and address human factors around critical decision-making during ICU airway management.

Efficacy and Tolerability of Adjunctive Intravenous Sodium Nitroprusside Treatment for Outpatients With Schizophrenia: A Randomized Clinical Trial.

Importance: Antipsychotic medications for the treatment of schizophrenia have limitations, and new treatments are needed. A prior pilot investigation suggested that adjunctive sodium nitroprusside (SNP) administered intravenously had rapid efficacy in the treatment of patients with schizophrenia. Objective: To determine the efficacy and tolerability of intravenous SNP infused at a rate of 0.5 µg/kg/min for 4 hours in patients with schizophrenia with some degree of treatment resistance. Design, Setting, and Participants: Multicenter, randomized, double-blind acute treatment study using a sequential parallel comparison design conducted in two 2-week phases at 4 academic medical centers beginning May 20, 2015, and ending March 31, 2017. Participants were adults 18 to 65 years of age with a diagnosis of schizophrenia as confirmed by the Structured Clinical Interview for DSM-IV, taking antipsychotic medication for at least 8 weeks, and had at least 1 failed trial of an antipsychotic medication within the past year. A total of 90 participants consented, 60 participants enrolled, and 52 participants were included in the analyses. A modified intent-to-treat analysis was used. Interventions: Participants were randomized in a 1:1:1 ratio to 1 of 3 treatment sequences: SNP and SNP, placebo and SNP, and placebo and placebo. The SNP and SNP group received SNP in phase 1 and SNP in phase 2 for the purpose of blinding, but the data from phase 2 were not included in the results. The placebo and SNP group received placebo in phase 1 and SNP in phase 2. If there was no response to placebo in phase 1, data from phase 2 were included in the analyses. The placebo and placebo group received placebo in both phases; if there was no response to placebo in phase 1, data from phase 2 were included in the analyses. Main Outcomes and Measures: Effectiveness of SNP compared with placebo in improving Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores across each 2-week phase. Results: Fifty-two participants (12 women and 40 men) were included in the study. In the SNP and SNP group, the mean (SD) age was 47.1 (10.5) years. In the placebo and SNP group, the mean (SD) age was 45.9 (12.3) years. In the placebo and placebo group, the mean (SD) age was 40.4 (11.0) years. There were no significant differences between the SNP and placebo groups at baseline or in change from baseline for PANSS-total (weighted ß = -1.04; z = -0.59; P = .57), PANSS-positive (weighted ß = -0.62; z = -0.93; P = .35), or PANSS-negative (weighted ß = -0.12; z = -0.19; P = .85) scores. No significant differences in safety or tolerability measures were identified. Conclusions and Relevance: Although intravenous SNP is well tolerated, it was not an efficacious adjunctive treatment of positive or negative symptoms of psychosis among outpatients with schizophrenia with prior history of treatment resistance. Trial Registration: ClinicalTrials.gov identifier: NCT02164981.

Oxygen saturation determined from deep muscle, not thenar tissue, is an early indicator of central hypovolemia in humans.

OBJECTIVE: To compare the responses of noninvasively measured tissue oxygen saturation (StO2) and calculated muscle oxygen tension (PmO2) to standard hemodynamic variables for early detection of imminent hemodynamic instability during progressive central hypovolemia in humans. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Sixteen healthy human volunteers. INTERVENTIONS: Progressive lower body negative pressure (LBNP) to onset of cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Noninvasive measurements of blood pressures, heart rate, and stroke volume were obtained during progressive LBNP with simultaneous assessments of StO2, PmO2, and muscle oxygen saturation (SmO2). Forearm SmO2 and PmO2 were determined with a novel near infrared spectroscopic measurement device (UMMS) and compared with thenar StO2 measured by a commercial device (HT). All values were normalized to the duration of LBNP exposure required for cardiovascular collapse in each subject (i.e., LBNP maximum). Stroke volume was significantly decreased at 25% of LBNP maximum, whereas blood pressure was a late indicator of imminent cardiovascular collapse. PmO2 (UMMS) was significantly decreased at 50% of maximum LBNP while SmO2 (UMMS) decreased at 75% of maximum LBNP. Thenar StO2 (HT) showed no statistical change throughout the entire LBNP protocol. CONCLUSIONS: Spectroscopic assessment of forearm muscle PO2 and SmO2 provides noninvasive and continuous measures that are early indicators of impending cardiovascular collapse resulting from progressive reductions in central blood volume.

Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans.

Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2 and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. SmO2 and SV were significantly decreased during the first LBNP level (-15 mmHg), whereas HR and BP were late indicators of impending cardiovascular collapse. SmO2 declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2 is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2 is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.

Airway management in critical illness.

Airway management in the ICU can be complicated due to many factors including the limited physiologic reserve of the patient. As a consequence, the likelihood of difficult mask ventilation and intubation increases. The incidence of failed airways and of cardiac arrest related to airway instrumentation in the ICU is much higher than that of elective intubations performed in the operating room. A thorough working knowledge of the devices available for the management of the difficult airway and recommended rescue strategies is paramount in avoiding bad patient outcomes. In this review, we will provide a conceptual framework for airway assessment, with an emphasis on assessment of the patient with limited cervical spine movement or injury and of morbidly obese patients. Furthermore, we will review the devices that are available for airway management in the ICU, and discuss controversies surrounding interventions like cricoid pressure and the use of muscle relaxants in the critically ill patient. Finally, strategies for the safe extubation of patients with known difficult airways will be provided.

Comparison of intramuscular and venous blood pH, PCO(2) and PO(2) during rhythmic handgrip exercise.

Oxygen and acid-base status during exercise is well established for the lungs, large arteries and veins. However, values for these parameters in exercising muscle are less frequently reported. In this study we examined the relationship between intramuscular PO(2), pH, PCO(2) and the comparable venous values during rhythmic isometric handgrip exercise at target levels of 15%, 30% and 45% of maximum voluntary contraction (MVC). A small fiber optic sensor was inserted into the flexor digitorum profundus (FDP) muscle for continuous measurement of intramuscular (IM) PO(2), pH and PCO(2). Venous blood samples were taken from the forearm every minute during each exercise bout. IM pH and PCO(2) were similar to their venous counterparts at baseline, but the difference between IM and venous values increased when exercise exceeded 30% MVC. During exercise at 15% MVC and greater, venous PO(2) declined from 40 to 21 Torr (approximately 5.3 to 2.8 kPa). IM PO(2) declined from 24 to 8 Torr with 15% MVC, and approached 0 Torr at 30% MVC and 45% MVC. IM pH declined rapidly when IM PO(2) reached 10 Torr and continued to decrease with increasing exertion, despite an IM PO(2) near 0 Torr.

Microvascular response to transfusion in elective spine surgery.

AIM: To investigate the microvascular (skeletal muscle tissue oxygenation; SmO2) response to transfusion in patients undergoing elective complex spine surgery. METHODS: After IRB approval and written informed consent, 20 patients aged 18 to 85 years of age undergoing > 3 level anterior and posterior spine fusion surgery were enrolled in the study. Patients were followed throughout the operative procedure, and for 12 h postoperatively. In addition to standard American Society of Anesthesiologists monitors, invasive measurements including central venous pressure, continual analysis of stroke volume (SV), cardiac output (CO), cardiac index (CI), and stroke volume variability (SVV) was performed. To measure skeletal muscle oxygen saturation (SmO2) during the study period, a non-invasive adhesive skin sensor based on Near Infrared Spectroscopy was placed over the deltoid muscle for continuous recording of optical spectra. All administration of fluids and blood products followed standard procedures at the Hospital for Special Surgery, without deviation from usual standards of care at the discretion of the Attending Anesthesiologist based on individual patient comorbidities, hemodynamic status, and laboratory data. Time stamps were collected for administration of colloids and blood products, to allow for analysis of SmO2 immediately before, during, and after administration of these fluids, and to allow for analysis of hemodynamic data around the same time points. Hemodynamic and oxygenation variables were collected continuously throughout the surgery, including heart rate, blood pressure, mean arterial pressure, SV, CO, CI, SVV, and SmO2. Bivariate analyses were conducted to examine the potential associations between the outcome of interest, SmO2, and each hemodynamic parameter measured using Pearson's correlation coefficient, both for the overall cohort and within-patients individually. The association between receipt of packed red blood cells and SmO2 was performed by running an interrupted time series model, with SmO2 as our outcome, controlling for the amount of time spent in surgery before and after receipt of PRBC and for the inherent correlation between observations. Our model was fit using PROC AUTOREG in SAS version 9.2. All other analyses were also conducted in SAS version 9.2 (SAS Institute Inc., Cary, NC, United States). RESULTS: Pearson correlation coefficients varied widely between SmO2 and each hemodynamic parameter examined. The strongest positive correlations existed between ScvO2 (P = 0.41) and SV (P = 0.31) and SmO2; the strongest negative correlations were seen between albumin (P = -0.43) and cell saver (P = -0.37) and SmO2. Correlations for other laboratory parameters studied were weak and only based on a few observations. In the final model we found a small, but significant increase in SmO2 at the time of PRBC administration by 1.29 units (P = 0.0002). SmO2 values did not change over time prior to PRBC administration (P = 0.6658) but following PRBC administration, SmO2 values declined significantly by 0.015 units (P < 0.0001). CONCLUSION: Intra-operative measurement of SmO2 during large volume, yet controlled hemorrhage, does not show a statistically significant correlation with either invasive hemodynamic, or laboratory parameters in patients undergoing elective complex spine surgery.