Pharmacokinetics of Total and Unbound Cefazolin during Veno-Arterial Extracorporeal Membrane Oxygenation: A Case Report.

Extra-corporeal membrane oxygenation (ECMO) therapy could affect effective drug concentrations via adsorption onto the oxygenator or associated circuit. We describe a case of a 25-year-old female who required a veno-arterial ECMO therapy for refractory cardiac arrest due to massive pulmonary embolism. She had mild renal dysfunction as a result of the cardiac arrest. A total of 2 g of intravenous cefazolin 8-hourly was administered. Pre- and post-oxygenator blood samples were collected at 0, 1, 4, and 8 h post antibiotic administration. Samples were analyzed for total and unbound cefazolin concentrations. Protein binding was ∼60%. Clearance was reduced due to impaired renal function. The pharmacokinetics of cefazolin appear to not be affected by ECMO therapy and dosing adjustment may not be required.

Low-dose clonidine infusion to improve sleep in postoperative patients in the high-dependency unit. A randomised placebo-controlled single-centre trial.

PURPOSE: Dexmedetomidine increases sleep and reduces delirium in postoperative patients, but it is expensive and requires a monitored environment. Clonidine, another α 2-agonist, is cheaper and is used safely for other purposes in wards. We assessed whether clonidine would improve sleep in postoperative high-dependency unit (HDU) patients. METHODS: The Clonidine at Low dosage postoperatively to Nocturnally Enhance Sleep (CLONES) study was a double-blind, placebo-controlled, parallel-group pilot effectiveness randomised trial involving adult elective surgery HDU patients in a single academic hospital. Patients received clonidine 0.3 µg/kg/h or saline placebo on the night of surgery. The primary outcome was total sleep time measured using a consumer actigraphy/photoplethysmography device. RESULTS: Of the 83 randomised patients, three had no data available, leaving 80 (39 clonidine, 41 placebo) in the intention-to-treat analysis, modified for missing data. Median patient ages of the groups were similar (61 and 59 years), as were other baseline characteristics. Clonidine patients had a mean of 100.8 (95% confidence interval [CI] 38.2-163.4) minutes (p = 0.002) longer total sleep time (mean 497.2 vs. 396.4 min) and reported better sleep overall. Delirium was only observed in one patient prior to study drug infusion, and none at the end of the study. Safety outcomes were not different. Four clonidine patients had their medication ceased due to bradycardia and hypotension that required no additional treatment. CONCLUSION: Among postoperative elective surgical patients admitted to HDU, low-dose non-titrated clonidine, compared to placebo, was associated with longer and subjectively better-quality sleep.

Delayed Tracheoesophageal Fistula and Refractory Respiratory Failure Caused by Inhalation Burns and Emergency Venovenous ECMO to Facilitate Its Management: A Case Report.

Acquired tracheoesophageal fistulae are uncommon in burn patients but can occur as a complication of inhalation injury. We report a case of a 30-yr-old male patient presenting after suffering from inhalation and 25% total body surface area burns. On postburns day 14, he developed a massive tracheoesophageal fistula causing refractory acute respiratory failure. Veno-venous extracorporeal membrane (VV ECMO) oxygenation was initiated without systemic anticoagulation via bi-femoral cannulation under transthoracic echocardiography guidance. He underwent successful 5-hr apnoeic ventilation-assisted surgical repair of the fistula via a right posterolateral thoracotomy. ECMO was discontinued after 36 hr, and he was discharged to the ward after 33 d in the intensive care unit. Inhalation burn injury can cause a delayed life-threatening tracheoesophageal fistula. Surgical repair can be successfully performed for this condition. VV- ECMO can be used to facilitate prolonged apnoeic surgery and to manage refractory respiratory failure due to this condition.

Cost-effectiveness of extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: A modelling study.

Background: Extracorporeal cardiopulmonary resuscitation (E-CPR) is a method of CPR that passes the patient's blood through an extracorporeal membrane oxygenation (ECMO) device to provide mechanical haemodynamic and oxygenation support in cardiac arrest patients who are not responsive to conventional CPR (C-CPR). E-CPR is being adopted rapidly worldwide despite the absence of high quality trial data and its substantial cost. Published cost-effectiveness data for E-CPR are scarce. Methods: We developed a mathematical model to estimate the cost-effectiveness of E-CPR relative to C-CPR in adult patients with refractory out-of-hospital cardiac arrest (OHCA). The model was a combination of a decision tree for the acute treatment phase and a Markov model for long-term periods. Cost-effectiveness was evaluated from the Australian health system perspective over lifetime. Cost-effectiveness was expressed as Australian dollars (AUD, 2021 value) per quality-adjusted life year (QALY) gained. Variables were parameterised using published data. Probabilistic and univariate sensitivity analyses were performed. Results: The incremental cost-effectiveness ratio (ICER) of E-CPR was estimated to be AUD 45,716 per QALY gained over lifetime (95% uncertainty range 22,102-292,904). The cost-effectiveness of E-CPR was most sensitive to the outcome of the therapy. Conclusion: E-CPR has median ICER that is below common accepted willingness-to-pay thresholds. Local factors within the health care system need to be considered to determine the feasibility of implementing an effective E-CPR program.

Impact of fasting on the gastric volume of critically ill patients before extubation: a prospective observational study using gastric ultrasound.

Background: A period of fasting before tracheal extubation of ventilated patients in the ICU is common practice, aiming to reduce gastric volume and aspiration risk. As the volume of gastric content is unknown at the time of extubation, the efficacy of this practice is uncertain. Methods: A prospective, observational study using gastric ultrasound was undertaken. Images were obtained at four time points: (i) at baseline, with gastric feeds running; (ii) after suctioning of gastric contents through a gastric tube; (iii) after a 4 h period with no gastric feed running; and (iv) after both a 4 h fasting period and gastric tube suctioning. The primary outcome was the proportion of patients classed as low risk of aspiration with each intervention, using qualitative and quantitative gastric ultrasound. Results: Fifty-four patients in the ICU were enrolled. Forty-four (81%) subjects had images that were suitable for analysis. Suctioning of stomach content through a gastric tube and fasting were equivalent with 39/44 (88.6%) and 5/44 (11.4%) subjects classified as low risk and at risk of aspiration, respectively. A period of fasting followed by suction resulted in 41/44 (93.2%) patients being at low risk. Conclusions: Suctioning of stomach contents through the gastric tube and a 4 h fasting period appear equivalent at reducing gastric volume below a safe threshold. A small percentage did not reach the threshold despite all interventions.

Staff perceptions of military chemical-biological-radiological-nuclear (CBRN) air-purifying masks during a simulated clinical task in the context of SARS-CoV-2.

Air-purifying full-face masks, such as military chemical-biological-radiological-nuclear masks, might offer superior protection against severe acute respiratory syndrome coronavirus 2 compared to disposable polypropylene P2 or N95 masks. In addition, disposable masks are in short supply, while military chemical-biological-radiological-nuclear masks can be disinfected then reused. It is unknown whether such masks might be appropriate for civilians with minimal training in their use. Accordingly, we compared the Australian Defence Force in-service chemical-biological-radiological-nuclear Low Burden Mask (AirBoss Defense, Newmarket, Canada) with polypropylene N95 masks and non-occlusive glasses worn during simulated tasks performed by civilian clinicians in an Australian tertiary referral hospital intensive care unit. After brief training in the use of the Low Burden Mask, participants undertook a simulated cardiac arrest scenario. Previous training with polypropylene N95 masks had been provided. Evaluation of 10 characteristics of each mask type were recorded, and time to mask application was assessed. Thirty-three participants tested the Low Burden Mask, and 28 evaluated polypropylene N95 masks and glasses. The Low Burden Mask was donned more quickly: mean time 7.0 (standard deviation 2.1) versus 18.3 (standard deviation 6.7) seconds; P = 0.0076. The Low Burden Mask was rated significantly higher in eight of the 10 assessed criteria, including ease of donning, comfort (initially and over a prolonged period), fogging, seal, safety while removing, confidence in protection, and overall. Visibility and communication ability were rated equally highly for both systems. We conclude that this air-purifying full-face mask is acceptable to clinicians in a civilian intensive care unit. It enhances staff confidence, reduces waste, and is likely to be a lower logistical burden during a prolonged pandemic. Formal testing of effectiveness is warranted.

Pharmacokinetics of fluconazole and ganciclovir as combination antimicrobial chemotherapy on ECMO: a case report.

Extracorporeal membrane oxygenation (ECMO) can affect antimicrobial pharmacokinetics. This case report describes a 33-year-old male with newly diagnosed acquired immunodeficiency syndrome presenting in acute severe type 1 respiratory failure. On investigation, the patient had positive cultures for Candida albicans from respiratory specimens and high blood cytomegalovirus titres, and required venovenous ECMO therapy for refractory respiratory failure. Intravenous fluconazole (6 mg/kg, 24-h) and ganciclovir (5 mg/kg, 12-h) was commenced. Pre-oxygenator, post-oxygenator and arterial blood samples were collected after antibiotic administration, and were analysed for total fluconazole and ganciclovir concentrations. Although there was a 40% increase in the volume of distribution for fluconazole relative to healthy volunteers, the pharmacodynamic targets for prophylaxis were still met. The area under the curve exposure of ganciclovir (50.78 mg•h/L) achieved target thresholds. The ECMO circuit had no appreciable effect on achievement of therapeutic exposures of fluconazole and ganciclovir.

Increasing ventilator surge capacity in COVID 19 pandemic: design, manufacture and in vitro-in vivo testing in anaesthetized healthy pigs of a rapid prototyped mechanical ventilator.

OBJECTIVE: The advent of new technologies has made it possible to explore alternative ventilator manufacturing to meet the worldwide shortfall for mechanical ventilators especially in pandemics. We describe a method using rapid prototyping technologies to create an electro-mechanical ventilator in a cost effective, timely manner and provide results of testing using an in vitro-in vivo testing model. RESULTS: Rapid prototyping technologies (3D printing and 2D cutting) were used to create a modular ventilator. The artificial manual breathing unit (AMBU) bag connected to wall oxygen source using a flow meter was used as air reservoir. Controlled variables include respiratory rate, tidal volume and inspiratory: expiratory (I:E) ratio. In vitro testing and In vivo testing in the pig model demonstrated comparable mechanical efficiency of the test ventilator to that of standard ventilator but showed the material limits of 3D printed gears. Improved gear design resulted in better ventilator durability whilst reducing manufacturing time (< 2-h). The entire cost of manufacture of ventilator was estimated at 300 Australian dollars. A cost-effective novel rapid prototyped ventilator for use in patients with respiratory failure was developed in < 2-h and was effective in anesthetized, healthy pig model.

Pharmacokinetics of Sulfamethoxazole and Trimethoprim During Venovenous Extracorporeal Membrane Oxygenation: A Case Report.

Extracorporeal membrane oxygenation (ECMO) therapy could affect drug concentrations via adsorption onto the oxygenator and/or associated circuit. We describe a case of a 33-year-old man with severe respiratory failure due to Pneumocystis jirovecii infection on a background of recently diagnosed human immunodeficiency virus infection. He required venovenous ECMO therapy for refractory respiratory failure. Intravenous sulfamethoxazole-trimethoprim (100 and 20 mg/kg/day) was administered in a dosing regimen every 6 hours. Pre-oxygenator, post-oxygenator, and arterial blood samples were collected after antibiotic administration and were analyzed for total sulfamethoxazole and trimethoprim concentrations. The peak sulfamethoxazole and trimethoprim concentrations were 122 mg/L and 5.3 mg/L, respectively. The volume of distribution for sulfamethoxazole was 0.37 and 2.30 L/kg for trimethoprim. The clearance for sulfamethoxazole was 0.35 ml/minute/kg and for trimethoprim was 1.64 ml/minute/kg. The pharmacokinetics of sulfamethoxazole and trimethoprim appear not to be affected by ECMO therapy, and dosing adjustment may not be required.

Successful Resuscitation of Maternal Cardiac Arrest With Disseminated Intravascular Coagulation Guided by Rotational Thromboelastometry and Transesophageal Echocardiography: A Case Report.

We present a case of maternal cardiac arrest during an elective cesarean delivery. Transesophageal echocardiography identified a large pulmonary artery mass, and guided resuscitation efforts. After return of spontaneous circulation, the patient developed disseminated intravascular coagulation with massive hemorrhage. Blood product selection and volume replacement were guided by rotational thromboelastometry and transesophageal echocardiography, respectively. Correction of coagulopathy was observed clinically and confirmed by rotational thromboelastometry. The patient fully recovered without neurological deficit.