A pilot feasibility, safety and biological efficacy multicentre trial of therapeutic hypercapnia after cardiac arrest: study protocol for a randomized controlled trial

BACKGROUND: Cardiac arrest causes ischaemic brain injury. Arterial carbon dioxide tension (PaCO2) is a major determinant of cerebral blood flow. Thus, mild hypercapnia in the 24 h following cardiac arrest may increase cerebral blood flow and attenuate such injury. We describe the Carbon Control and Cardiac Arrest (CCC) trial. METHODS/DESIGN: The CCC trial is a pilot multicentre feasibility, safety and biological efficacy randomized controlled trial recruiting adult cardiac arrest patients admitted to the intensive care unit after return of spontaneous circulation. At admission, using concealed allocation, participants are randomized to 24 h of either normocapnia (PaCO2 35 to 45 mmHg) or mild hypercapnia (PaCO2 50 to 55 mmHg). Key feasibility outcomes are recruitment rate and protocol compliance rate. The primary biological efficacy and biological safety measures are the between-groups difference in serum neuron-specific enolase and S100b protein levels at 24 h, 48 h and 72 h. Secondary outcome measure include adverse events, in-hospital mortality, and neurological assessment at 6 months. DISCUSSION: The trial commenced in December 2012 and, when completed, will provide clinical evidence as to whether targeting mild hypercapnia for 24 h following intensive care unit admission for cardiac arrest patients is feasible and safe and whether it results in decreased concentrations of neurological injury biomarkers compared with normocapnia. Trial results will also be used to determine whether a phase IIb study powered for survival at 90 days is feasible and justified. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000690853 .

Cerebral oxygenation in mechanically ventilated early cardiac arrest survivors: The impact of hypercapnia

BACKGROUND : Optimal cerebral oxygenation is considered fundamental to cerebral protection in cardiac arrest (CA) patients. Hypercapnia increases cerebral blood flow and may also improve cerebral oxygenation. It is uncertain, however, whether this effect occurs in mechanically ventilated early survivors of CA. METHODS: We enrolled mechanically ventilated resuscitated patients within 36 h of their cardiac arrest. We performed a prospective double cross-over physiological study comparing the impact of normocapnia (PaCO2 35-45 mmHg) vs. mild hypercapnia (PaCO2 45-55 mmHg) on regional cerebral tissue oxygen saturation (SctO2) assessed by near infrared spectroscopy (NIRS).RESULTS: We studied seven adult CA patients with a median time to return of spontaneous circulation of 28 min at a median of 26 h and 30 min after CA. During normocapnia (median EtCO2 of 32 mmHg [30-41 mmHg] and PaCO2 of 37 mmHg [32-45 mmHg]) the median NIRS-derived left frontal SctO2 was 61% [52-65%] and the right frontal SctO2 was 61% [54-68%]. However, during mild hypercapnia (median EtCO2 of 49 mmHg [40-57 mmHg] and PaCO2 of 52 mmHg [43-55 mmHg) the median left frontal SctO2 increased to 69% [59-78%] and the right frontal SctO2 increased to 73% [61-76%])(p = 0.001, for all comparisons). CONCLUSION: During the early post-resuscitation period, in mechanically ventilated CA patients, mild hypercapnia increases cerebral oxygenation as assessed by NIRS. Further investigations of the effect of prolonged mild hypercapnia on cerebral oxygenation and patient outcomes appear justified.

Using an evidence-based care bundle to improve Thai emergency nurses' knowledge of care for patients with severe traumatic brain injury

There is known variation in Thai nurses' knowledge regarding the best available evidence for care of patients with severe traumatic brain injury. The purpose of this study was to examine the impact of an evidence-based care bundle on Thai emergency nurses' knowledge regarding management of patients with severe traumatic brain injury. A pre-test/post-test design was used. The study intervention was an evidence-based care bundle for initial nursing management of patients with severe traumatic brain injury. Data were collected from 31 Registered Nurses using multiple choice questions. Results revealed a statistically significant improvement in overall knowledge scores after care bundle implementation (p < 0.001). There were statistically significant improvements in five areas of knowledge: understanding of target end-tidal carbon dioxide levels (p < 0.001), implications of hypocapnia in severe traumatic brain injury (p = 0.01), implications of hypercapnia in severe traumatic brain injury (p = 0.02), importance of maintaining head and neck in neutral position (p = 0.05), and administration of sedatives and analgesics in severe traumatic brain injury (p = 0.01). This study suggested that implementation of an evidence-based care bundle improved emergency nurses' knowledge regarding management of patients with severe traumatic brain injury.

A pilot assessment of alpha-stat vs pH-stat arterial blood gas analysis after cardiac arrest

PURPOSE: Resuscitated cardiac arrest (CA) patients typically receive therapeutic hypothermia, but arterial blood gases (ABGs) are often assessed after adjustment to 37°C (alpha-stat) instead of actual body temperature (pH-stat). We sought to compare alpha-stat and pH-stat assessment of PaO2 and PaCO2 in such patients. MATERIALS AND METHODS: Using ABG data obtained during the first 24 hours of intensive care unit admission, we determined the impact of measured alpha vs calculated pH-stat on PaO2 and PaCO2 on patient classification and outcomes for CA patients. RESULTS: We assessed 1013 ABGs from 120 CA patients with a median age of patients 66 years (interquartile range, 50-76). Median alpha-stat PaO2 changed from 122 (95-156) to 107 (82-143) mm Hg with pH-stat and median PaCO2 from 39 (34-46) to 35 (30-41) mm Hg (both P < .001). Using the categories of hyperoxemia, normoxemia, and hypoxemia, pH-stat estimation of PaO2 reclassified approximately 20% of patients. Using the categories of hypercapnia, normocapnia, and hypocapnia, pH stat estimation of PaCO2 reclassified approximately 40% of patients. The mortality of patients in different PaO2 and PaCO2 categories was similar for pH-stat and alpha-stat. CONCLUSIONS: Using the pH-stat method, fewer resuscitated CA patients admitted to intensive care unit were classified as hyperoxemic or hypercapnic compared with alpha-stat. These findings suggest an impact of ABG assessment methodology on PaO2, PaCO2 , and patient classification but not on associated outcomes.