Shay McGuinness

Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome.

CONTEXT The novel influenza A(H1N1) pandemic affected Australia and New Zealand during the 2009 southern hemisphere winter. It caused an epidemic of critical illness and some patients developed severe acute respiratory distress syndrome (ARDS) and were treated with extracorporeal membrane oxygenation (ECMO). OBJECTIVES To describe the characteristics of all patients with 2009 influenza A(H1N1)-associated ARDS treated with ECMO and to report incidence, resource utilization, and patient outcomes. DESIGN, SETTING, AND PATIENTS An observational study of all patients (n = 68) with 2009 influenza A(H1N1)-associated ARDS treated with ECMO in 15 intensive care units (ICUs) in Australia and New Zealand between June 1 and August 31, 2009. MAIN OUTCOME MEASURES Incidence, clinical features, degree of pulmonary dysfunction, technical characteristics, duration of ECMO, complications, and survival. RESULTS Sixty-eight patients with severe influenza-associated ARDS were treated with ECMO, of whom 61 had either confirmed 2009 influenza A(H1N1) (n = 53) or influenza A not subtyped (n = 8), representing an incidence rate of 2.6 ECMO cases per million population. An additional 133 patients with influenza A received mechanical ventilation but no ECMO in the same ICUs. The 68 patients who received ECMO had a median (interquartile range [IQR]) age of 34.4 (26.6-43.1) years and 34 patients (50%) were men. Before ECMO, patients had severe respiratory failure despite advanced mechanical ventilatory support with a median (IQR) Pao(2)/fraction of inspired oxygen (Fio(2)) ratio of 56 (48-63), positive end-expiratory pressure of 18 (15-20) cm H(2)O, and an acute lung injury score of 3.8 (3.5-4.0). The median (IQR) duration of ECMO support was 10 (7-15) days. At the time of reporting, 48 of the 68 patients (71%; 95% confidence interval [CI], 60%-82%) had survived to ICU discharge, of whom 32 had survived to hospital discharge and 16 remained as hospital inpatients. Fourteen patients (21%; 95% CI, 11%-30%) had died and 6 remained in the ICU, 2 of whom were still receiving ECMO. CONCLUSIONS During June to August 2009 in Australia and New Zealand, the ICUs at regional referral centers provided mechanical ventilation for many patients with 2009 influenza A(H1N1)-associated respiratory failure, one-third of whom received ECMO. These ECMO-treated patients were often young adults with severe hypoxemia and had a 21% mortality rate at the end of the study period.

Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care

BACKGROUND The safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported. METHODS We randomly assigned 7000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4, Voluven) in 0.9% sodium chloride or 0.9% sodium chloride (saline) for all fluid resuscitation until ICU discharge, death, or 90 days after randomization. The primary outcome was death within 90 days. Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy. RESULTS A total of 597 of 3315 patients (18.0%) in the HES group and 566 of 3336 (17.0%) in the saline group died (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P=0.26). There was no significant difference in mortality in six predefined subgroups. Renal-replacement therapy was used in 235 of 3352 patients (7.0%) in the HES group and 196 of 3375 (5.8%) in the saline group (relative risk, 1.21; 95% CI, 1.00 to 1.45; P=0.04). In the HES and saline groups, renal injury occurred in 34.6% and 38.0% of patients, respectively (P=0.005), and renal failure occurred in 10.4% and 9.2% of patients, respectively (P=0.12). HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001). CONCLUSIONS In patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy. (Funded by the National Health and Medical Research Council of Australia and others; CHEST ClinicalTrials.gov number, NCT00935168.).

Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients

BACKGROUND The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury. METHODS We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization. RESULTS Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P<0.001). CONCLUSIONS In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days. (ClinicalTrials.gov number, NCT00221013.)

Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial

IMPORTANCE Saline (0.9% sodium chloride) is the most commonly administered intravenous fluid; however, its use may be associated with acute kidney injury (AKI) and increased mortality. OBJECTIVE To determine the effect of a buffered crystalloid compared with saline on renal complications in patients admitted to the intensive care unit (ICU). DESIGN AND SETTING Double-blind, cluster randomized, double-crossover trial conducted in 4 ICUs in New Zealand from April 2014 through October 2014. Three ICUs were general medical and surgical ICUs; 1 ICU had a predominance of cardiothoracic and vascular surgical patients. PARTICIPANTS All patients admitted to the ICU requiring crystalloid fluid therapy were eligible for inclusion. Patients with established AKI requiring renal replacement therapy (RRT) were excluded. All 2278 eligible patients were enrolled; 1152 of 1162 patients (99.1%) receiving buffered crystalloid and 1110 of 1116 patients (99.5%) receiving saline were analyzed. INTERVENTIONS Participating ICUs were assigned a masked study fluid, either saline or a buffered crystalloid, for alternating 7-week treatment blocks. Two ICUs commenced using 1 fluid and the other 2 commenced using the alternative fluid. Two crossovers occurred so that each ICU used each fluid twice over the 28 weeks of the study. The treating clinician determined the rate and frequency of fluid administration. MAIN OUTCOMES AND MEASURES The primary outcome was proportion of patients with AKI (defined as a rise in serum creatinine level of at least 2-fold or a serum creatinine level of ≥3.96 mg/dL with an increase of ≥0.5 mg/dL); main secondary outcomes were incidence of RRT use and in-hospital mortality. RESULTS In the buffered crystalloid group, 102 of 1067 patients (9.6%) developed AKI within 90 days after enrollment compared with 94 of 1025 patients (9.2%) in the saline group (absolute difference, 0.4% [95% CI, -2.1% to 2.9%]; relative risk [RR], 1.04 [95% CI, 0.80 to 1.36]; P = .77). In the buffered crystalloid group, RRT was used in 38 of 1152 patients (3.3%) compared with 38 of 1110 patients (3.4%) in the saline group (absolute difference, -0.1% [95% CI, -1.6% to 1.4%]; RR, 0.96 [95% CI, 0.62 to 1.50]; P = .91). Overall, 87 of 1152 patients (7.6%) in the buffered crystalloid group and 95 of 1110 patients (8.6%) in the saline group died in the hospital (absolute difference, -1.0% [95% CI, -3.3% to 1.2%]; RR, 0.88 [95% CI, 0.67 to 1.17]; P = .40). CONCLUSIONS AND RELEVANCE Among patients receiving crystalloid fluid therapy in the ICU, use of a buffered crystalloid compared with saline did not reduce the risk of AKI. Further large randomized clinical trials are needed to assess efficacy in higher-risk populations and to measure clinical outcomes such as mortality. TRIAL REGISTRATION clinicaltrials.gov Identifier: ACTRN12613001370796.

Nasal high-flow therapy delivers low level positive airway pressure

Background The aim of this prospective study was to determine whether a level of positive airway pressure was generated in participants receiving nasal high flow (NHF) delivered by the Optiflow™ system (Fisher and Paykel Healthcare Ltd, Auckland, New Zealand) in a cardiothoracic and vascular intensive care unit (ICU). Methods Nasopharyngeal airway pressure was measured in 15 postoperative cardiac surgery adult patients who received both NHF and standard facemask therapy at a flow rate of 35 litre min−1. Measurements were repeated in the open mouth and closed mouth positions. Mean airway pressure was determined by averaging the pressures at the peak of inspiration of each breath within a 1 min period, allowing the entire pressure profile of each breath to be included within the calculation. Results Low level positive pressure was demonstrated with NHF at 35 litre min−1 with mouth closed when compared with a facemask. NHF generated a mean nasopharyngeal airway pressure of mean (sd) 2.7 (1.04) cm H2O with the mouth closed. Airway pressure was significantly higher when breathing with mouth closed compared with mouth open (P≤0.0001). Conclusions This study demonstrated that a low level of positive pressure was generated with NHF at 35 litre min−1 of gas flow. This is consistent with results obtained in healthy volunteers. Australian Clinical Trials Registry www.actr.org.au ACTRN012606000139572.

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.

Extracorporeal Membrane Oxygenation for Treating Severe Cardiac and Respiratory Failure in Adults: Part 2: Technical Considerations

i a N THIS SECOND OF 2 articles on the use of extracorporeal membrane oxygenation (ECMO) for treating severe cardiac nd respiratory failure in adults, the physiology, technical coniderations, and complications of this technique are reviewed. lthough ECMO remains a technically and logistically deanding undertaking, recent advances in the design of circuit omponents, particularly the oxygenator, have improved the ase of use and durability of the technique, such that extracororeal support can be maintained relatively safely for several eeks.

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)

Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery

Background Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. Methods In a trial with a 2‐by‐2 factorial design, we randomly assigned patients who were scheduled to undergo coronary‐artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. Results Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fishers exact test). Conclusions Among patients undergoing coronary‐artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.)

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).