The ACURASYS study of atracurium vs placebo in ARDS: three ml rapid intravenous infusion of 15 mg of cis-atracurium besylate or placebo was administered, followed by a continuous infusion of 37.5 mg per hour for 48 hours. There appeared to be benefits in the intervention group, although the mechanisms are not clear. Further studies are needed.
BACKGROUND: In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. METHODS: In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. RESULTS: The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. CONCLUSIONS: In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)
Aeromedical retrieval specialists in Scotland developed a simple, cheap, effective in-flight cooling protocol using intravenous (IV) cold Hartmann’s solution and chemical cooling packs. Fluids cooled in a fridge (4°C) were transported in an insulated cool box; the patient was sedated, paralysed and intubated, and controlled ventilation started. The patient was then cooled by IV infusion of 30 ml/kg of cold Hartmann’s. Chemical ice packs were activated and placed in the axillae and groin. The time interval between successful resuscitation and the patient being retrieved and flown to an Intensive Care Unit (ICU) was at least 3.5 h. Cooled patients had a mean decrease in body temperature during retrieval compared to patients not cooled (−1.6 °C vs. +0.9 °C, p = 0.005) and a lower body temperature on ICU arrival (34.1 °C vs. 36.4 °C, p = 0.05). Two of the 5 cooled patients achieved target temperature (<34 °C) before ICU arrival. No complications of in-flight cooling were reported. Not the only way to cool down in Scotland In-flight cooling after out-of-hospital cardiac arrest Resuscitation. 2010 Aug;81(8):1041-2
An Australian randomised controlled trial assessed the effect of pre-hospital cooling (using 2 litres ice cold Hartmann’s) of post-cardiac arrest patients on functional status at hospital discharge. The intervention group were marginally cooler on arrival but did not have improved outcomes.
The authors conclude: In adults who have been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation, paramedic cooling with a rapid infusion of large-volume, ice-cold intravenous fluid decreased core temperature at hospital arrival but was not shown to improve outcome at hospital discharge compared with cooling commenced in the hospital. Induction of Therapeutic Hypothermia by Paramedics After Resuscitation From Out-of-Hospital Ventricular Fibrillation Cardiac Arrest Circulation. 2010 Aug 17;122(7):737-42 Free Full Text
One issue from this study was that relatively short urban pre-hospital transport times meant some patients did not get the full two litres, and some had already received room temperature fluids during the cardiac arrest resuscitation. The authors suggest further study should involved initiating cooling during the arrest. In fact a European study has done just that, using a device call a RhinoChill (a portable transnasal cooling device) to lower temperature during arrest in a randomised controlled trial. This trial showed pre-hospital intra-arrest transnasal cooling is safe and feasible and is associated with a significant improvement in the time intervals required to cool patients.
Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness) Circulation. 2010 Aug 17;122(7):729-36
A thought provoking article in Critical Care Medicine outlines basic science, animal, and human studies that suggest oestrogen may have a protective effect in a wide range of critical illnesses from cardiac arrest to trauma to stroke. It urges clinical trials of sex hormones, some of which are underway. Regarding traumatic brain injury, the authors state: “To date, studied interventions to treat the effects of secondary injury, such as induced hypothermia or sedative-hypnotic coma, have had disappointing results… Clearly, EMS (or emergency department) infusion of a single IV bolus of estrogen, a therapy shown in the laboratory to be a strong, direct, easy-to-deliver antioxidant, antiapoptotic, and anti-inflammatory intervention, has a much better chance of decreasing the severity of injury.”
Bold? Let’s see if studies such as this one show this intervention to be so beneficial. Rationale for routine and immediate administration of intravenous estrogen for all critically ill and injured patients Critical Care Medicine. 38(10):S620-S629, October 2010
Applying best evidence using simple easily remembered tools appeals to my small and busy brain. A system of minimising the impact of intensive care on long term brain function is proposed using an ABCDE mnemonic: awakening, spontaneous breathing trials, coordinating these two with target-based sedation, delirium monitoring and scoring, and early mobility therapy / exercise. A screening, prevention, and restoration model for saving the injured brain in intensive care unit survivors Critical Care Medicine Oct 2010;38(10):S683-S691
The UK’s National Institute for Health and Clinical Excellence (NICE) has produced guidelines on delirium.
Delirium (sometimes called ‘acute confusional state’) is a common clinical syndrome characterised by disturbed consciousness, cognitive function or perception, which has an acute onset and fluctuating course.
Some snippets from the guideline include:
If indicators of delirium are identified, carry out a clinical assessment based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria or short Confusion Assessment Method (short CAM) to confirm the diagnosis.
In critical care or in the recovery room after surgery, CAM-ICU should be used. A healthcare professional who is trained and competent in the diagnosis of delirium should carry out the assessment.
If there is difficulty distinguishing between the diagnoses of delirium, dementia or delirium superimposed on dementia, treat for delirium first.
If a person with delirium is distressed or considered a risk to themselves or others and verbal and non-verbal de-escalation techniques are ineffective or inappropriate, consider giving short- term (usually for 1 week or less) haloperidol or olanzapine.
The CAM-ICU assessment tool is demonstrated in the video below, which is found along with other helpful delirium resources at http://www.icudelirium.co.uk
24 difficult to wean patients underwent three spontaneous breathing trials in random order, with PA catheter monitoring in place. T-piece spontaneous ventilation was compared with pressure support ventilation 7 cmH20 without PEEP, and with pressure support ventilation 7 cmH20 with 5 cmH20 PEEP. T-piece was associated with higher SBT failure rates and more patient effort, left ventricular failure, and smaller tidal volumes. The study suggests that in selected difficult-to-wean patients, clinical and physiological responses differ depending on the type of SBT used to ascertain whether or not a patient is ready for extubation. Of note, the authors did not extubate the patients who succeeded a PSV trial, because it has been shown that a spontaneous breathing trial using T-piece mimics the work of breathing performed after extubation, and an extubation failure is associated with high mortality. Physiological comparison of three spontaneous breathing trials in difficult-to-wean patients Intensive Care Med. 2010 Jul;36(7):1171-9
Results from 24 studies on dexmedetomidine were assessed in a meta-analysis to determine the effect on ICU length of stay. The authors concluded that the limited evidence suggests that dexmedetomidine might reduce length of ICU stay in some critically ill patients, but the risk of bradycardia was significantly higher when both a loading dose and high maintenance doses (>0.7 μg/kg/h) were used. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med. 2010 Jun;36(6):926-39
Bloods sampled from both femoral vein and SVC-sited catheters in critically ill patients showed good correlation in lactate levels but the oxygen saturation was not so reliable, with >5% variation in more than 50% and >15% variation in some patients. The authors suggest one reason is that the femoral catheter tip usually sits in the iliac vein and samples blood prior to the mixing of blood returning from intra-abdominal organs. They advise caution in using SfvO2 to guide resuscitation when narrow end points are used, as this may lead to inappropriate vasoactive drug or blood component therapy.
Femoral-Based Central Venous Oxygen Saturation Is Not a Reliable Substitute for Subclavian/Internal Jugular-Based Central Venous Oxygen Saturation in Patients Who Are Critically Ill Chest. 2010 Jul;138(1):76-83
A CME article in Critical Care Medicine summarises the literature on ARDS (including its limitations) and provides evidence based recommendations on what to do about severe hypoxaemia. They summarise:
For life-threatening hypoxaemia, initial management with a recruitment manoeuvre and/or high PEEP should be undertaken if plateau airway pressures and lack of barotrauma allow. If not, or if these are not effective, then proceed to the prone position or HFOV. If hypoxemia still persists, then consider the administration of inhaled NO. If NO fails, then glucocorticoids can then be administered. For elevated plateau airway pressures when tidal volumes are 4 mL/kg, consider prone positioning or HFOV. For life- threatening respiratory acidosis, consider the use of a buffer or continuous veno-venous hemofiltration. It is most important to assess for objective physiologic improvement in the appropriate time period for each intervention. If no benefit is evident, then the therapy should be discontinued to minimise harm and delay in the initiation of another therapy. If the patient continues to have life-threatening hypoxemia, acidosis, or elevated plateau airway pressures, then consider ECMO or extracorporeal carbon dioxide removal.
