On the Transition from Control Modes to Spontaneous Modes during ECMO.

The transition from control modes to spontaneous modes is ubiquitous for mechanically ventilated patients yet there is little data describing the changes and patterns that occur to breathing during this transition for patients on ECMO. We identified high fidelity data among a diverse cohort of 419 mechanically ventilated patients on ECMO. We examined every ventilator change, describing the differences in >30,000 sets of original ventilator observations, focused around the time of transition from control modes to spontaneous modes. We performed multivariate regression with mixed effects, clustered by patient, to examine changes in ventilator characteristics within patients, including a subset among patients with low compliance (<30 milliliters (mL)/centimeters water (cmH2O)). We found that during the transition to spontaneous modes among patients with low compliance, patients exhibited greater tidal volumes (471 mL (364,585) vs. 425 mL (320,527); p < 0.0001), higher respiratory rate (23 breaths per minute (bpm) (18,28) vs. 18 bpm (14,23); p = 0.003), greater mechanical power (elastic component) (0.08 mL/(cmH2O × minute) (0.05,0.12) vs. 0.05 mL/(cmH2O × minute) (0.02,0.09); p < 0.0001) (range 0 to 1.4), and lower positive end expiratory pressure (PEEP) (6 cmH2O (5,8) vs. 10 cmH2O (8,11); p < 0.0001). For patients on control modes, the combination of increased tidal volume and increased respiratory rate was temporally associated with significantly low partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (p < 0.0001). These changes in ventilator parameters warrant prospective study, as they may be associated with worsened lung injury.

Predicting mortality in cardiogenic shock secondary to ACS requiring short-term mechanical circulatory support: The ACS-MCS score.

OBJECTIVE: To identify predictors of 30-day all-cause mortality for patients with cardiogenic shock secondary to acute coronary syndrome (ACS-CS) who require short-term mechanical circulatory support (ST-MCS). BACKGROUND: ACS-CS mortality is high. ST-MCS is an attractive treatment option for hemodynamic support and stabilization of deteriorating patients. Mortality prediction modeling for ACS-CS patients requiring ST-MCS has not been well-defined. METHODS: The Utah Cardiac Recovery (UCAR) Shock database was used to identify patients admitted with ACS-CS requiring ST-MCS devices between May 2008 and August 2018. Pre-ST-MCS clinical, laboratory, echocardiographic, and angiographic data were collected. The primary endpoint was 30-day all-cause mortality. A weighted score comprising of pre-ST-MCS variables independently associated with 30-day all-cause mortality was derived and internally validated. RESULTS: A total of 159 patients (mean age, 61 years; 78% male) were included. Thirty-day all-cause mortality was 49%. Multivariable analysis resulted in four independent predictors of 30-day all-cause mortality: age, lactate, SCAI CS classification, and acute kidney injury. The model had good calibration and discrimination (area under the receiver operating characteristics curve 0.80). A predictive score (ranging 0-4) comprised of age ≥ 60 years, pre-ST-MCS lactate ≥2.5 mmol/L, AKI at time of ST-MCS implementation, and SCAI CS stage E effectively risk stratified our patient population. CONCLUSION: The ACS-MCS score is a simple and practical predictive score to risk-stratify CS secondary to ACS patients based on their mortality risk. Effective mortality risk assessment for ACS-CS patients could have implications on patient selection for available therapeutic strategy options.

Characteristics of Patients Managed without Positive Pressure Ventilation While on Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has expanding indications for cardiopulmonary resuscitation including severe acute respiratory distress syndrome (ARDS). Despite the adjunct of ECMO for patients with severe ARDS, they often have prolonged mechanical ventilation and are subject to many of its inherent complications. Here, we describe patients who were cannulated for venovenous (VV) ECMO and were taken off positive pressure ventilation. METHODS: This is a primary analysis of patients admitted at a tertiary medical center between the dates of August 2014 to January 2020 who were cannulated to ECMO for refractory respiratory failure. We included all patients ≥18 years old. Patients who were extubated or had a tracheostomy and taken off positive pressure while on ECMO were classified as "off positive pressure ventilation (PPV)" and were compared to patients who remained "on PPV" while on ECMO. Primary outcome was survival to hospital discharge. Secondary outcomes were ventilator free days at 30 days and 60 days after ECMO cannulation, time from cannulation to date of first out-of-bed (OOB), and hospital length of stay (LOS). Patient characteristics were derived from routine clinical information in the electronic health record (EHR). Categorical characteristics were compared using chi-square test or Fisher exact test. Continuous characteristics were compared using independent samples t-test or Wilcoxon-Mann-Whitney test. p-values were reported from all analysis. RESULTS: Sixty-five patients were included in this retrospective analysis. Forty-eight were managed on ECMO with PPV and 17 patients were removed from PPV. Patients removed from PPV had significantly higher lung injury scores prior to cannulation (2.5 ± 0.6 vs. 1.04 ± 0.3; p = 0.031) and non-significantly longer duration of ventilation prior to ECMO (6.1 days ± 2.1 vs. 5.0 days ± 01.1; p = 0.634). One hundred percent (100%) of patients removed from PPV survived to hospital discharge compared to 45% who received PPV throughout their duration of ECMO management (p < 0.001). The mean ventilator free days at day 60 was 15 with PPV and 36 without PPV (p = 0.003). The average duration from cannulation to mobilization (i.e., out-of-bed) was 18 days with PPV and 7 days without PPV (p = 0.015). CONCLUSIONS: Patients taken off PPV while on ECMO had a very high likelihood of survival to discharge and were mobilized in half as many days. While this likely reflects patient selection, the benefit of early mobilization is well documented and the approach of extubating while on ECMO warrants further investigation.

Toward Point-of-Care Drug Quality Assurance in Developing Countries: Comparison of Liquid Chromatography and Infrared Spectroscopy Quantitation of a Small-Scale Random Sample of Amoxicillin.

Substandard antibiotics are thought to be a major threat to public health in developing countries and a cause of antimicrobial resistance. However, assessing quality outside of a laboratory setting, using simple equipment, is challenging. The aim of this study was to validate the use of a portable Fourier transform infrared (FT-IR) spectrometer for the identification of substandard antibiotics. Results are presented for amoxicillin packages from Haiti, Ghana, Sierra Leone, Democratic Republic of Congo, India, Papua New Guinea, and Ethiopia collected over the course of 6 months in 2017, including two field trips with the FT-IR to Ghana and Sierra Leone. Canadian samples were used as a control. Regarding drug quality, of 290 individual capsules of amoxicillin analyzed, 13 were found to be substandard with total active pharmaceutical ingredients (API) lying outside the acceptable range of 90-110%. Of these 13, four were below 80% API. The FT-IR reliably identified these outliers and was found to yield results in good agreement with the established pharmacopeia liquid chromatography protocol. We conclude that the portable FT-IR may be suitable to intercept substandard antibiotics in developing countries where more sophisticated techniques are not readily available.

An Analysis of Substandard Propofol Detected in Use in Zambian Anesthesia.

BACKGROUND: In early 2015, clinicians throughout Zambia noted a range of unpredictable adverse events after the administration of propofol, including urticaria, bronchospasm, profound hypotension, and most predictably an inadequate depth of anesthesia. Suspecting that the propofol itself may have been substandard, samples were procured and sent for testing. METHODS: Three vials from 2 different batches were analyzed using gas chromatography-mass spectrometry methods at the John L. Holmes Mass Spectrometry Facility. RESULTS: Laboratory gas chromatography-mass spectrometry analysis determined that, although all vials contained propofol, its concentration differed between samples and in all cases was well below the stated quantity. Two vials from 1 batch contained only 44% ± 11% and 54% ± 12% of the stated quantity, whereas the third vial from a second batch contained only 57% ± 9%. The analysis found that there were no hexane-soluble impurities in the samples. CONCLUSIONS: None of the analyzed vials contained the stated amount of propofol; however, our analysis did not detect additional contaminants that would explain the adverse events reported by clinicians. Our results confirm the presence of substandard propofol in Zambia; however, anecdotal accounts of substandard anesthetic medicines in other countries abound and warrant further investigation to provide estimates of the prevalence and scope of this global problem.

Dual-spray hydrogen/deuterium exchange (HDX) reactions: A new method of probing protein structure.

RATIONALE: Traditionally, hydrogen/deuterium exchange (HDX) reactions are done in the solution phase. This usually involves incubating the protein with a suitable deuterating agent then acidifying the solution to quench the reaction. A more efficient method may be to conduct the reaction within the ion source of a mass spectrometer and subsequently analyze the products. METHODS: Using the two electrospray emitters equipped on the Waters Synapt G1 mass spectrometer, HDX reactions were conducted within the ion source region in a controlled fashion ('dual-spray'). Peptide and protein solutions were electrosprayed through one emitter and the deuterating agent D2 O through the secondary electrospray emitter. For the relatively small peptides, Phe-Leu-Glu-Glu-Leu and oxytocin, the yield of products was calculated using deconvolution functions. Electrospray ionization (ESI) charge-state distributions and average number of deuterium exchanges were used to probe secondary and tertiary structures of ubiquitin, lysozyme, and cytochrome c in their native and unfolded states. RESULTS: Clear shifts in isotope distributions indicated HDX occurring within the ion source. By ion mobility, simultaneous deuterium exchange for two isobaric species, the oxytocin monomer and dimer, was observed. For denatured ubiquitin, the 12+ and 13+ charge states have a lower average number of exchanges relative to the lower charge states which indicates that these charge states have segments which restrict the access of D2 O. Lysozyme has a linear relationship between the charge state and the average number of exchanges, indicating that lysozyme becomes increasingly unfolded as the charge state increases. The dual-spray HDX method was paired to high-performance liquid chromatography (HPLC) to demonstrate the applicability of the technique for probing gas-phase structures in protein mixtures. CONCLUSIONS: ESI droplets formed from a secondary emitter penetrate primary ESI droplets and change the solvent composition. Dual-spray HDX is demonstrated to be a more efficient method for probing the structure of proteins than solution-phase HDX since the acid quenching step can be surpassed. Copyright © 2016 John Wiley & Sons, Ltd.

Fatal Bacterial Meningitis Possibly Associated with Substandard Ceftriaxone--Uganda, 2013.

The burden of disease from bacterial meningitis is highest in low-income countries (1). Early initiation of antibiotic therapy is important in reducing the risk for mortality. Current treatment guidelines recommend the use of an expanded-spectrum cephalosporin (cefotaxime or ceftriaxone) (2), but these therapies increasingly are limited by drug resistance, and are threatened by the proliferation of substandard and falsified medicines (3,4). In February 2013, a case of bacterial meningitis following a middle ear infection was diagnosed in an adolescent at the Mulago National Referral Hospital in Kampala, Uganda. Once-daily treatment with 2 g of intravenous ceftriaxone administered according to guidelines failed, and the patient died. To determine whether the patient's treatment failure and subsequent death might be related to the ceftriaxone product administered, a sealed vial similar to the one administered to the patient was analyzed at the University of Ottawa, Canada, and was found to contain only 0.455 g of the drug, not 1 g as stated by the manufacturer. This would have resulted in subtherapeutic dosing. Substandard medicines are a global problem that disproportionately affects low-income countries, leading to fatal consequences and promoting the emergence of drug resistance (4).

When is death inevitable after emergency laparotomy? Analysis of the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: In an era of increasing demands to provide high-quality health care, surgeons need an accurate preoperative risk assessment tool to facilitate informed decision-making for themselves and their patients. Emergency laparotomy procedures have a high risk profile, but the currently available risk-assessment models for emergency laparotomy are either unreliable (eg, small sample size or single center study), difficult to calculate preoperatively, or are specific to the geriatric population. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Program database (2005 to 2009) was used to develop logistic regression models for 30-day mortality after emergency laparotomy. Two models were created, one with the knowledge of the postoperative diagnosis and one without. Models' calibration and discrimination were judged using the receiver operating characteristics curves and the Hosmer-Lemeshow test. RESULTS: There were 37,553 patients who had undergone emergency laparotomy, with a 14% mortality rate. The American Society of Anesthesiologists classification system, functional status, sepsis, and age were the variables most significantly associated with mortality. Patients older than 90 years of age, with an American Society of Anesthesiologists class V, septic shock, dependent functional status, and abnormal white blood cell count have a <10% probability of survival. CONCLUSIONS: The models developed in this study have a high discriminative ability to stratify the operative risk in a broad range of acute abdominal emergencies. These data will assist surgeons, patients, and their families in making end-of-life decisions in the face of medical futility with greater certainty when emergency surgery is being contemplated.