Shock 的治療目標 Early goal-directed therapy
Early goal-directed therapy: do we have a definitive answer?
by Daniel De Backer| Jean-Louis Vincent
Early goal-directed therapy (EGDT) for the treatment of septic shock was first proposed in 2001 by Rivers et al. [1]. These authors reported that patients with hypotension refractory to a fluid challenge of 20–30 ml/kg of crystalloids over 30 min or with plasma lactate levels of at least 4 mEq/l and who were treated to restore and maintain a central venous oxygen saturation (ScvO2) of greater than 70 % had lower 28-day mortality rates than control patients (33 vs 49 %). That publication generated considerable enthusiasm but also much debate. The resuscitation protocol was incorporated into the Surviving Sepsis Campaign (SSC) guidelines [2] and several uncontrolled studies reported similar improvements in outcome [3–5]. However, concerns were raised about the single-center nature of the trial, the limited sample size (263 patients), the multiple interventions proposed in the EGDT package making it difficult to differentiate which was most effective, and the potential influence of confounding factors including the increased presence of doctors at the bedside of patients randomized to the intervention.
Three large-scale multicenter studies published in 2014 and 2015 [6–8] were unable to replicate the results of the Rivers study, but is there a plausible explanation for this? Among the important differences between the trials, the mortality rate in the control groups in the recent trials was markedly lower than that in the Rivers study (Table 1). In addition, ScvO2 values in the study groups were markedly reduced (to an average of 49 %) in the Rivers trial but were already within the greater than 70 % target zone in the three other trials. One explanation may be that Rivers et al. treated a special patient population with severe comorbidities and/or who presented quite late to the emergency department. Another possible explanation is that there has been a marked improvement in prehospital and initial care of patients with septic shock, maybe as a direct result of the Rivers trial and the SSC guidelines. However, adequacy of antibiotic treatment and amounts of fluid administered prior to randomization do not seem to account for these differences (Table 1).
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This patient selection issue does not challenge the internal validity of these recent trials, but clearly raises questions about their external validity. These trials have indicated that patients with low severity septic shock who rapidly respond to therapy do not benefit from routine EGDT. However, the results of the Rivers trial have not been invalidated as patients with high disease severity and low ScvO2 were not included in these recent trials. EGDT may still be beneficial in the most severely ill patients, especially when less experienced staff who may appreciate using simple protocols are in charge.
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Post-resuscitation care: ERC–ESICM guidelines 2015 - EDITORIAL
The ERC-ESICM guidelines on post-resuscitation care are intended to be practical and more didactic, i.e. they tell the clinician exactly what to do. They cover the whole post-cardiac arrest patient pathway and include elements of pre-hospital care, in-hospital treatment and finally rehabilitation.
Animal studies suggest that after return of spontaneous circulation (ROSC), hyperoxia may worsen neurological injury. Clinical data on neurological injury are conflicting but a recent study of air versus supplemental oxygen in ST-elevation myocardial infarction showed deleterious effects of oxygen treatment. As soon as arterial blood oxygen saturation can be monitored reliably, the ERC-ESICM recommendation is to titrate the inspired oxygen concentration to maintain the arterial blood oxygen saturation in the range of 94–98 %. As yet, there are no prospective data defining an optimal plasma carbon dioxide target in the post-cardiac arrest patient, and observational data are inconsistent. Until further data are available the recommendation is to aim for normocarbia.
If cardiac arrest has been caused by an acute coronary occlusion, achieving coronary reperfusion as soon as possible is a high priority. Emergent cardiac catheterisation laboratory evaluation (and immediate percutaneous coronary intervention (PCI) if required) should be performed in adult patients with ROSC after out-of-hospital cardiac arrest (OHCA) of suspected cardiac origin with ST-elevation (STE) on the ECG. This recommendation is relatively non-controversial; the management of those patients with a likely cardiac cause of their cardiac arrest but without STE on the ECG is less well defined. In general, it is reasonable to discuss and consider emergent cardiac catheterisation laboratory evaluation after ROSC in patients with the highest risk of a coronary cause for their cardiac arrest. The ERC-ESICM guidelines include recommendations on the timing of computed tomography (CT) scanning in relation to coronary catheterisation and these are summarised in a post-cardiac arrest algorithm.
The prevention of post-ROSC hyperthermia and the implementation of targeted temperature management (TTM) remains a strong recommendation in the ERC-ESICM guidelines. There is no international consensus on the precise target temperature—the current recommendation is to maintain a constant temperature in the range 32–36 °C for 24 h.
Predicting the final neurological outcome of those who remain comatose after resuscitation from cardiac arrest is problematic and it is now generally accepted that decisions about withdrawal of life-sustaining treatment (WLST) have been made far too early. The ERC and ESICM have already published guidelines on prognostication after cardiac arrest and these have been incorporated into the 2015 post-resuscitation care guidelines. The principles of prognostication are that it is generally delayed until at least 3 days after cardiac arrest and it is multimodal.
Many cardiac arrest survivors have cognitive and emotional problems long after hospital discharge. To date, there have been few structured programmes to rehabilitate these patients and this is a component of the patient pathway that can be improved considerably. The ERC-ESICM guidelines provide recommendations on the follow-up care for post-cardiac arrest patients.
Since 2010, considerable progress in clinical research has created important advances, making these post-resuscitation guidelines immediately applicable in many patients. However, there are still knowledge gaps, which require further investigation. Temperature management is probably the field in which most questions remain unsolved. Should we use a specific cooling technique? What is the best sedation strategy during cooling? Who are the best candidates for a lower target temperature target (32–34 °C)? Should we start cooling during transport to hospital? As early pneumonia is very frequent in cooled patients, should we give prophylactic antibiotics? Ongoing clinical studies might provide definitive conclusions in the very near future. The optimal management of post-resuscitation circulatory failure also remains controversial. Although some clinical data suggest 75 mmHg as a target for mean arterial pressure, this should be further investigated in prospective studies. The use of steroids during the post-resuscitation shock also requires further exploration. Brain injury is the cornerstone of outcome: new imaging and electrophysiological investigations will help to refine the neuroprognostication strategy that has been proposed. Finally, follow-up care for survivors is now recommended but we need high-level evidence for this rehabilitation phase.
While further science is awaited, we sincerely hope that these 2015 guidelines will help intensive care clinicians to treat their post-cardiac arrest patients.
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