Therapeutic hypothermia post out-of-hospital cardiac arrest - more questions than answers?

Nearly a decade since the introduction of therapeutic hypothermia to the ICU for cooling out-of-hospital cardiac arrest patients, key questions remain unanswered: when should cooling be initiated, how rapidly should the patient be cooled and using which device? The Time to Target Temperature study group provides important baseline data on the striking direct relationship between body temperature and survival from out-of-hospital cardiac arrest.Patients post out-of-hospital cardiac arrest (OHCA) are common admissions to the ICU. Therapeutic hypothermia has been shown to improve both survival and neurological outcome for OHCA patients surviving to reach the ICU and now forms part of routine post-resuscitation care. The Time to Target Temperature (TTTT) study group presents key observations on the relationship between body temperature and outcome following OHCA [1], yet ultimately are we left with more questions than answers on therapeutic hypothermia?Nearly a decade ago two landmark papers fundamentally changed the practice of post-resuscitation care. The Hypothermia after Cardiac Arrest study group [2] and Bernard and colleagues [3] not only demonstrated the benefit of cooling OHCA patients but also highlighted how hugely effective the therapy was, with a number needed to treat of seven patients and six patients, respectively, for survival. Such impressive therapeutic benefit is rarely seen in medical practice, let alone in critical care medicine. A key difference between these two studies was the time from return of spontaneous circulation (ROSC) to the onset of cooling. The time to reach the target temperature (<34°C) varied greatly from immediately post ROSC to over 16 hours post ROSC and yet the therapeutic benefit of cooling was still evident. The TTTT group demonstrated that the change in body temperature during the period from ROSC to cooling initiation has a direct relationship on survival [1].Since 2002 few studies have examined the optimum method, rate of cooling and timing of initiation. Little is known about the mechanism of action of therapeutic hypothermia. Whilst animal evidence strongly suggests that early cooling, especially intra-arrest, is beneficial, few human studies have demonstrated a benefit from early cooling. Early cooling, in the prehospital or emergency department setting, has significant technical challenges and may distract from the basic principles of resuscitation. Yet emerging evidence suggests that cold reperfusion at the time of ROSC may confer greater benefit in limiting ischaemic-reperfusion injury. For cold reperfusion to occur, very rapid intra-arrest cooling would be required and some novel intranasal cooling devices have shown promising initial results [4]. Previous studies have demonstrated that most OHCA patients are relatively hypothermic in the prehospital phase, and whether initiating cooling, maintaining hypothermia or even normothermia would confer survival benefit remains unknown [5]. Although OHCA patients are naturally hypothermic in the immediate phase following collapse, they may still benefit from early therapeutic cooling.The TTTT group elegantly demonstrate that OHCA patients destined for a favourable outcome re-warm rapidly post OHCA, are warmer at cooling initiation and take longer to reach the target therapeutic temperature than OHCA patients destined for an unfavourable out-come. This observation appears contradictory to the notion that earlier, faster cooling favours a positive outcome post OHCA. No definitive explanation can yet be offered for the TTTT group finding. Unfavourable OHCA patients would appear to lack the homeostatic mechanism to regulate body temperature and appear to cool faster than favourable patients. Underlying mechanisms are postulated to include ischaemic hypothalamic damage and the inability of hypoxic mitochondria to generate heat.Clearly, the underlying cardiovascular and neurological processes involved with regulating body temperature post OHCA need further research and explanation. A better understanding of the mechanisms through which therapeutic hypothermia confers neuroprotection and survival would allow the therapy to be optimised, potentially saving many more lives. Despite nearly a decade of research since the routine introduction of therapeutic hypothermia to the ICU, a key question remains: what is the optimum time point to initiate therapeutic hypothermia post OHCA?Further prospective trials are urgently required to provide answers to the key questions surrounding cooling post OHCA, particularly to determine the optimum means, timing and rate of cooling. The TTTT group study provides a platform with important baseline data for planning this vital future research.     

Ventilator-associated tracheobronchitis (VAT): questions,answers, and a new paradigm?

Nosocomial lower respiratory tract infections are a common cause of morbidity and mortality in intensive care unit (ICU) patients. Although many studies have investigated the management and prevention of ventilator-associated pneumonia (VAP), few have focused on ventilator-associated tracheobronchitis (VAT). In this issue of Critical Care, Nseir and coworkers present interesting data from a randomized controlled study of antimicrobial therapy for VAT. Patients randomly assigned to antibiotic therapy had more mechanical ventilation-free days (P < 0.001), fewer episodes of VAP (13% versus 47%; P < 0.001), and a lower ICU mortality rate (18% versus 47%; P = 0.05) than those without antibiotic therapy. Although this study has limitations, the data suggest that VAT may be an important risk factor for VAP or overlap with early VAP. More importantly, targeted antibiotic therapy for VAT may improve patient outcomes and become a new paradigm for prevention or early therapy for VAP.     

Headaches and pineal cyst: a (more than) coincidental relationship?

Pineal cysts are common findings in neuroimaging studies. The cysts are more frequent in women in their third decade of life. Pineal cysts can be symptomatic, headache is the most common symptom. The pineal gland has important physiological implications in humans, but little is known about the impact of pineal cysts in human physiology. We report 5 headache patients with pineal cyst, 4 women, 1 man, mean age 37.6, mean cyst diameter 10.1 mm. Two patients had migraine without aura, 1 migraine with aura, 1 chronic migraine, and 1 hemicrania continua. Three patients had strictly unilateral headaches. We hypothesize pineal cysts may be not incidental in headache patients, inducing an abnormal melatonin secretion.     

Perioperative statins: more than lipid-lowering?

Preliminary evidence indicates that statin drugs may be beneficial when given in the perioperative period. Although more studies are needed to draw firm conclusions, the acute nonlipid pleiotropic effects of statins may improve patient outcomes, especially for patients at the highest risk.     

Vasopressin and ischaemic heart disease: more than coronary vasoconstriction?

During advanced vasodilatory shock, arginine vasopressin (AVP) is increasingly used to restore blood pressure and thus to reduce catecholamine requirements. The AVP-related rise in mean arterial pressure is due to systemic vasoconstriction, which, depending on the infusion rate, may also reduce coronary blood flow despite an increased coronary perfusion pressure. In a murine model of myocardial ischaemia, Indrambarya and colleagues now report that a 3-day infusion of AVP decreased the left ventricular ejection fraction, ultimately resulting in increased mortality, and thus compared unfavourably with a standard treatment using dobutamine. The AVP-related impairment myocardial dysfunction did not result from the increased left ventricular afterload but from a direct effect on cardiac contractility. Consequently, the authors conclude that the use of AVP should be cautioned in patients with underlying cardiac disease.     

Residents’ clinical questions: How are they answered and are the answers helpful?

Objective

To assess residents’ clinical questions, where they get their answers, the utility of those answers, and if an evidence-based medicine (EBM) workshop improves the use of evidence-based electronic resources.

Design

Prospective observational cohort study.

Setting

Urban family medicine teaching clinics in Edmonton, Alta, in 2007.

Participants

First- and second-year family medicine residents training in the family medicine teaching units.

Methods

An observer recorded clinical questions posed by residents in clinic, the resources used to answer these questions, and how residents thought the answers modified practice. Resources were categorized broadly as colleagues, electronic, or paper. Answer utility was ranked in decreasing order as large change, small change, confirmed, expanded knowledge, or no help. Use of resources was compared before and after an EBM workshop, and between residents under normal supervision and those in semi-independent clinics.

Results

Thirty-eight residents from 5 sites were observed addressing 325 questions in 114 clinical half-day sessions (420 patients). Residents had 0.8 questions per patient and answered 83.4% of questions with 1 resource (range 1 to 6). Residents made 406 attempts to answer questions, using colleagues 65.5% of the time (93.6% were preceptors), electronic resources 20.7% of the time, and paper resources 13.8% of the time. Answers from colleagues were least likely to require secondary resources (F test, P < .001). The utility of answers from colleagues (F test, P = .002) was superior to that of answers from electronic resources, and this difference remained significantly higher in sensitivity analysis. The EBM workshop training did not influence electronic resource use (17.8% before and 15.1% after, Fisher-Freeman-Halton test, P = .18), but semi-independence from preceptors increased the use of electronic resources from 16.5% to 51.0% (Fisher-Freeman-Halton test, P < .001).

Conclusion

Residents have many questions during clinical practice. Preceptors were used more commonly than all other resources combined and were the most dependable resource for residents to obtain answers. Although an EBM workshop was not associated with increased use of electronic evidence-based resources, semi-independent work appeared to be.     

Antibiotic cycling: more than it might seem?

In the present battle against the rising tide of resistance, several interventions have been proposed to help control the situation. One of these is a process of planned antibiotic restriction, introduced through cycling drug selection based on local surveillance. Although such antibiotic cycling has been the subject of much discussion for 20 years, there are relatively few data available to assess its worth. A recent systematic review found only four studies worthy of inclusion and concluded that antibiotic cycling could not, at present, be promoted as a methodology to control resistance. This paper considers the complete literature and through demonstrating consistent benefits across the breadth and depth of the findings, suggests that whereas further work is required, nevertheless antibiotic cycling-as part of a suite of control measures-is a valid option.