Xenon – no bull?

Xenon, an inert ‘noble’ gas with proven anaesthetic properties, has possible neuroprotective properties and appears to be also cardioprotective in this small study of post-cardiac arrest patients. Its high viscosity affects airway resistance, resulting in higher peak pressures and the need for a strategy to avoid gas trapping (ie. longer expiratory times as with asthma). Apparently it’s expensive, but these results suggest further study is warranted.

Feasibility and Cardiac Safety of Inhaled Xenon in Combination With Therapeutic Hypothermia Following Out-of-Hospital Cardiac Arrest
Crit Care Med. 2013 Sep;41(9):2116-24


OBJECTIVES: Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients.

DESIGN: An open controlled and randomized single-centre clinical drug trial (clinicaltrials.gov NCT00879892).

SETTING: A multipurpose ICU in university hospital.

PATIENTS: Thirty-six adult out-of-hospital cardiac arrest patients (18-80 years old) with ventricular fibrillation or pulseless ventricular tachycardia as initial cardiac rhythm.

INTERVENTIONS: Patients were randomly assigned to receive either mild therapeutic hypothermia treatment with target temperature of 33°C (mild therapeutic hypothermia group, n = 18) alone or in combination with xenon by inhalation, to achieve a target concentration of at least 40% (Xenon + mild therapeutic hypothermia group, n = 18) for 24 hours. Thirty-three patients were evaluable (mild therapeutic hypothermia group, n = 17; Xenon + mild therapeutic hypothermia group, n = 16).

MEASUREMENTS AND MAIN RESULTS: Patients were treated and monitored according to the Utstein protocol. The release of troponin-T was determined at arrival to hospital and at 24, 48, and 72 hours after out-of-hospital cardiac arrest. The median end-tidal xenon concentration was 47% and duration of the xenon inhalation was 25.5 hours. The frequency of serious adverse events, including inhospital mortality, status epilepticus, and acute kidney injury, was similar in both groups and there were no unexpected serious adverse reactions to xenon during hospital stay. In addition, xenon did not induce significant conduction, repolarization, or rhythm abnormalities. Median dose of norepinephrine during hypothermia was lower in xenon-treated patients (mild therapeutic hypothermia group = 5.30 mg vs Xenon + mild therapeutic hypothermia group = 2.95 mg, p = 0.06). Heart rate was significantly lower in Xenon + mild therapeutic hypothermia patients during hypothermia (p = 0.04). Postarrival incremental change in troponin-T at 72 hours was significantly less in the Xenon + mild therapeutic hypothermia group (p = 0.04).

CONCLUSIONS: Xenon treatment in combination with hypothermia is feasible and has favorable cardiac features in survivors of out-of-hospital cardiac arrest.

Lowering the BP rapidly in ICH

ICH-iconIn our retrieval service case reviews, one thing that is that sure to generate discussion is what to do about the blood pressure in patients who present with intracranial haemorrhage and hypertension. We don’t want the bleeding to be worsened by higher blood pressure, but we don’t want to decrease cerebral perfusion pressure in patients who have raised intracranial pressure. Consensus guidelines exist for spontaneous intracerebral haemorrhage and subarachnoid haemorrhage, but they’re not based on strong data.

Here’s a study that attempted to provide more information. Intensive lowering to a target systolic of 140 mmHg within 1 hour was compared with lowering to a target of 180 mmHg. There was no significant reduction in the rate of the primary outcome of death or severe disability. The skeptic in me is disappointed there was no placebo arm. An ordinal analysis of modified Rankin scores favoured the intensive BP-lowering intervention, which means this study can be used by both those for and against intensive BP lowering to support their views.

As explained in an accompanying editorial, a number of factors may limit generalisability to Western practice, such as the predominant use of the alpha-blocking agent urapadil in the large numbers of Asian patients, a drug not available in the United States. Future publication of the ATACH-II trial using intravenous nicardipine will shed more light on this topic.

1. Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage
N Engl J Med. 2013 Jun 20;368(25):2355-65


BACKGROUND: Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known.

METHODS: We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physician’s choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups.

RESULTS: Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively.

CONCLUSIONS: In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure.

2. Blood pressure in intracerebral hemorrhage–how low should we go?
N Engl J Med. 2013 Jun 20;368(25):2426-7