Rachael Parke

A preliminary randomized controlled trial to assess effectiveness of nasal high-flow oxygen in intensive care patients.

OBJECTIVE: In a cardiothoracic and vascular intensive care unit, to compare nasal high-flow (NHF) oxygen therapy and standard high-flow face mask (HFFM) oxygen therapy in patients with mild to moderate hypoxemic respiratory failure. METHODS: In a prospective randomized comparative study, 60 patients with mild to moderate hypoxemic respiratory failure were randomized to receive NHF or HFFM. We analyzed the success of allocated therapy, noninvasive ventilation rate, and oxygenation. RESULTS: Significantly more NHF patients succeeded with their allocated therapy (P = .006). The rate of noninvasive ventilation in the NHF group was 3/29 (10%), compared with 8/27 (30%) in the HFFM group (P = .10). The NHF patients also had significantly fewer desaturations (P = .009). CONCLUSIONS: NHF oxygen therapy may be more effective than HFFM in treating mild to moderate hypoxemic respiratory failure.

The Effects of Flow on Airway Pressure During Nasal High-Flow Oxygen Therapy

BACKGROUND: Nasal high-flow oxygen therapy increases the mean nasopharyngeal airway pressure in adults, but the relationship between flow and pressure is not well defined. OBJECTIVE: To determine the relationship between flow and pressure with the Optiflow nasal high-flow oxygen therapy system. METHODS: We invited patients scheduled for elective cardiac surgery to participate. Measurements were performed with nasal high-flow oxygen at flows of 30, 40, and 50 L/min, with the patients mouth both open and closed. Pressures were recorded over one minute of breathing, and average flows were calculated via simple averaging. RESULTS: With the mouth closed, the mean ± SD airway pressures at 30, 40, and 50 L/min were 1.93 ± 1.25 cm H2O, 2.58 ± 1.54 cm H2O, and 3.31 ± 1.05 cm H2O, respectively. There was a positive linear relationship between flow and pressure. CONCLUSIONS: The mean nasopharyngeal pressure during nasal high-flow oxygen increases as flow increases. (Australian Clinical Trials Registry http://www.adhb.govt.nz/achicu/hot_2_airway_pressure.htm)

Pressures Delivered By Nasal High Flow Oxygen During All Phases of the Respiratory Cycle

BACKGROUND: Nasal high flow (NHF) oxygen therapy and CPAP are modes of noninvasive respiratory support used to improve respiratory function in multiple patient groups. Both therapies provide positive pressure, although this varies during the respiratory cycle. The purpose of this study was to measure and compare the airway pressure generated during different phases of the respiratory cycle in patients receiving NHF at various gas flows. METHODS: Patients scheduled for elective cardiac surgery were invited to participate. Nasopharyngeal pressure measurements were performed using NHF with gas flows of 30, 40, and 50 L/min. All measurements were performed in random order, with the subject breathing with mouth closed. RESULTS: During NHF the mean ± SD nasopharyngeal airway pressures were 1.5 ± 0.6, 2.2 ± 0.8, and 3.1 ± 1.2 at 30, 40, and 50 L/min using NHF. Analyses also determined the mean peak expiratory and mean expiratory plateau pressures. CONCLUSIONS: The expiratory pressure during NHF was higher than the mean pressure previously reported for NHF. This may account in part for the disproportional clinical effects seen with NHF. (Australian Clinical Trials Registry www.anzctr.org.au ACTRN12609000305224).

Open-label, phase II study of routine high-flow nasal oxygen therapy in cardiac surgical patients

BACKGROUND Respiratory complications after cardiac surgery increase morbidity, mortality, and length of stay. Studies suggest that routine delivery of positive airway pressure after extubation may be beneficial. We sought to determine whether the routine administration of nasal high-flow oxygen therapy (NHF) improves pulmonary function after cardiac surgery. METHODS A pragmatic randomized controlled trial; participants received either NHF (45 litre min(-1)) or usual care from extubation to Day 2 after surgery. The primary outcome was number of patients with / ratio ≥445 on Day 3 after surgery. The secondary outcomes included atelectasis score on chest X-ray; spirometry; intensive care and hospital length of stay; mortality on Day 28; oxygenation indices; escalation of respiratory support; and patient comfort. RESULTS We randomized 340 patients over 14 months. The number of patients with a / ratio of ≥445 on Day 3 was 78 (46.4%) in the NHF group vs 72 (42.4%) standard care [odds ratio (OR) 1.18, 95% confidence interval (CI) 0.77-1.81, P=0.45]. was reduced at both 4 h post-extubation and at 9 a.m. on Day 1 in the NHF group (5.3 vs 5.4 kPa, P=0.03 and 5.1 vs 5.3 kPa, P=0.03, respectively). Escalation in respiratory support at any time in the study occurred in 47 patients (27.8%) allocated to NHF compared with 77 (45%) standard care (OR 0.47, 95% CI 0.29-0.7, P=0.001). CONCLUSIONS Routine use of NHF did not increase / ratio on Day 3 but did reduce the requirement for escalation of respiratory support. TRIAL REGISTRATION Australia New Zealand Clinical Trials Registry www.anzctr.org.au (ACTRN12610000973011).

ASAP ECMO: Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation: a multi-centre study to optimise drug therapy during ECMO

BackgroundGiven the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO.Methods/DesignThis is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO.DiscussionThe evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure.Trial registrationACTRN12612000559819

Sodium bicarbonate infusion to reduce cardiac surgery-associated acute kidney injury: a phase II multicenter double-blind randomized controlled trial

Objectives:Cardiac surgery–associated acute kidney injury occurs in up to 50% of patients and is associated with increased mortality and morbidity. This study aimed to discover if perioperative urinary alkalinization with sodium bicarbonate infusion reduces the prevalence of cardiac surgery–associated acute kidney injury. Design:This study was a phase IIb multicenter double-blind randomized controlled trial. Setting:This study was conducted in three tertiary hospitals in New Zealand and Australia. Patients:A total of 427 patients scheduled to undergo elective cardiac surgery, who were at increased risk of development of cardiac surgery–associated acute kidney injury using recognized risk factors. Measurements and Main Results:Patients were randomly allocated to receive either sodium bicarbonate (n = 215) or sodium chloride (n = 212) infusion, commencing at the start of anesthesia, in a dose of 0.5 mEq/kg/hr for the first hour and then 0.2 mmol/kg/hr for 23 hours. The primary outcome measure was the number of patients with development of cardiac surgery–associated acute kidney injury, defined as an increase in creatinine greater than 25% or 0.5 mg/dL (44 µmol/L) from baseline to peak value within the first five postoperative days. Significant differences among the groups in both plasma and urinary biochemistry were achieved 6 hours after commencement of the infusion, and these changes persisted for more than 24 hours. A total of 100 out of 215 patients (47% [95% CI, 40%–53%]) in the sodium bicarbonate group and 93 of 212 patients (44% [95% CI, 37%–51%]) in the sodium chloride group with development of acute kidney injury within the first five postoperative days (p = 0.58). There were also no significant differences in ventilation hours, ICU or hospital length of stay, or mortality. Conclusions:Perioperative alkalinization of blood and urine using an infusion of sodium bicarbonate did not result in a decrease in the prevalence of acute kidney injury in patients following cardiac surgery.

A Binational Multicenter Pilot Feasibility Randomized Controlled Trial of Early Goal-Directed Mobilization in the ICU*

Objectives:To determine if the early goal-directed mobilization intervention could be delivered to patients receiving mechanical ventilation with increased maximal levels of activity compared with standard care. Design:A pilot randomized controlled trial. Setting:Five ICUs in Australia and New Zealand. Participants:Fifty critically ill adults mechanically ventilated for greater than 24 hours. Intervention:Patients were randomly assigned to either early goal-directed mobilization (intervention) or to standard care (control). Early goal-directed mobilization comprised functional rehabilitation treatment conducted at the highest level of activity possible for that patient assessed by the ICU mobility scale while receiving mechanical ventilation. Measurements and Main Results:The ICU mobility scale, strength, ventilation duration, ICU and hospital length of stay, and total inpatient (acute and rehabilitation) stay as well as 6-month post-ICU discharge health-related quality of life, activities of daily living, and anxiety and depression were recorded. The mean age was 61 years and 60% were men. The highest level of activity (ICU mobility scale) recorded during the ICU stay between the intervention and control groups was mean (95% CI) 7.3 (6.3–8.3) versus 5.9 (4.9–6.9), p = 0.05. The proportion of patients who walked in ICU was almost doubled with early goal-directed mobilization (intervention n = 19 [66%] vs control n = 8 [38%]; p = 0.05). There was no difference in total inpatient stay (d) between the intervention versus control groups (20 [15–35] vs 34 [18–43]; p = 0.37). There were no adverse events. Conclusions:Key Practice Points: Delivery of early goal-directed mobilization within a randomized controlled trial was feasible, safe and resulted in increased duration and level of active exercises.

Effect of Very-High-Flow Nasal Therapy on Airway Pressure and End-Expiratory Lung Impedance in Healthy Volunteers

BACKGROUND: Previous research has demonstrated a positive linear correlation between flow delivered and airway pressure generated by high-flow nasal therapy. Current practice is to use flows over a range of 30–60 L/min; however, it is technically possible to apply higher flows. In this study, airway pressure measurements and electrical impedance tomography were used to assess the relationship between flows of up to 100 L/min and changes in lung physiology. METHODS: Fifteen healthy volunteers were enrolled into this study. A high-flow nasal system capable of delivering a flow of 100 L/min was purpose-built using 2 Optiflow systems. Airway pressure was measured via the nasopharynx, and cumulative changes in end-expiratory lung impedance were recorded using the PulmoVista 500 system at gas flows of 30–100 L/min in increments of 10 L/min. RESULTS: The mean age of study participants was 31 (range 22–44) y, the mean ± SD height was 171.8 ± 7.5 cm, the mean ± SD weight was 69.7 ± 10 kg, and 47% were males. Flows ranged from 30 to 100 L/min with resulting mean ± SD airway pressures of 2.7 ± 0.7 to 11.9 ± 2.7 cm H2O. A cumulative and linear increase in end-expiratory lung impedance was observed with increasing flows, as well as a decrease in breathing frequency. CONCLUSIONS: Measured airway pressure and lung impedance increased linearly with increased gas flow. Observed airway pressures were in the range used clinically with face-mask noninvasive ventilation. Developments in delivery systems may result in this therapy being an acceptable alternative to face-mask noninvasive ventilation.

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial)☆

BACKGROUND In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. METHODS In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. RESULTS We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). CONCLUSIONS In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.

Sodium bicarbonate and renal function after cardiac surgery: a prospectively planned individual patient meta-analysis.

Background:The effect of urinary alkalinization in cardiac surgery patients at risk of acute kidney injury (AKI) is controversial and trial findings conflicting. Accordingly, the authors performed a prospectively planned individual patient data meta-analysis of the double-blind randomized trials in this field. Methods:The authors studied 877 patients from three double-blind, randomized controlled trials enrolled to receive either 24 h of intravenous infusion of sodium bicarbonate or sodium chloride. The primary outcome measure was a postoperative increase in serum creatinine concentration of greater than 25% or 0.5 mg/dl (> 44 &mgr;M/L) within the first five postoperative days. Secondary outcomes included the raw change in serum creatinine, greater than 50% and greater than 100% rises in serum creatinine, developing AKI (Acute Kidney Injury Network criteria), initiation of renal replacement therapy, morbidity, and mortality. Results:Patients were similar in demographics, comorbidities, and cardiac procedures. Sodium bicarbonate increased plasma bicarbonate (P < 0.001) and urine pH (P < 0.001). There were no differences in the development of the primary outcome (Bicarbonate 45% [39–51%] vs. Saline 42% [36–48%], P = 0.29). This result remained unchanged when controlling for study and covariates (odds ratio [OR], 99% confidence interval [CI]: Bicarbonate vs. Control, 1.11 [0.77–1.60], P = 0.45). There was, however, a significant study-adjusted benefit in elective coronary artery bypass surgery patients in terms of renal replacement therapy (Bicarbonate vs. Control, OR: 0.38 [99% CI: 0.25–0.58], P < 0.0001) and the development of an Acute Kidney Injury Network grade = 3 (Bicarbonate vs. Control, OR: 0.45 [99% CI: 0.43–0.48], P < 0.0001). Conclusions:Urinary alkalinization using sodium bicarbonate infusion is not associated with an overall lower incidence of AKI; however, it reduces severe AKI and need for renal replacement therapy in elective coronary artery bypass patients.