Critical care : the official journal of the Critical Care Forum
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Observational Study
Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: identifying at-risk patients.
Improved methods to optimize drug dosing in the critically ill are urgently needed. Traditional prescribing culture involves recognition of factors that mandate dose reduction (such as renal impairment), although optimizing drug exposure, through more frequent or augmented dosing, represents an evolving strategy. Elevated creatinine clearance (CLCR) has been associated with sub-therapeutic antibacterial concentrations in the critically ill, a concept termed augmented renal clearance (ARC). We aimed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients, while also examining demographic, physiological and illness severity characteristics that may help identify this phenomenon. ⋯ Diagnosis, illness severity and age, are likely to significantly influence renal drug elimination in the critically ill, and must be regularly considered in future study design and daily prescribing practice.
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Observational Study
Termination-of-resuscitation rule for emergency department physicians treating out-of-hospital cardiac arrest patients: an observational cohort study.
The 2010 cardiopulmonary resuscitation guidelines recommend emergency medical services (EMS) personnel consider prehospital termination-of-resuscitation (TOR) rules for out-of-hospital cardiac arrest (OHCA) following basic life support and/or advanced life support efforts in the field. However, the rate of implementation of international TOR rules is still low. Here, we aimed to develop and validate a new TOR rule for emergency department physicians to replace the international TOR rules for EMS personnel in the field. This rule aims to guide physicians in deciding whether to withhold further resuscitation attempts or terminate on-going resuscitation immediately after patient arrival. ⋯ We developed and validated a new TOR rule for emergency department physicians consisting of 3 prehospital variables (no prehospital ROSC, unshockable initial rhythm, and unwitnessed by bystanders) that is a >99% predictor of very poor outcome. However, the implementation of this new rule in other countries or EMS systems requires further validation studies.
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Editorial Comment
Immunotherapy - a potential new way forward in the treatment of sepsis.
A recent randomized controlled clinical trial of the immunostimulatory agent thymosin alpha-1 was conducted and showed a trend toward improved survival in patients receiving the drug (P = 0.06). Although this was a relatively small study and the exact mechanism of action of thymosin alpha-1 is not known, the present results further support the evolving concept that, as sepsis persists, a hypoinflammatory and immunosuppressive condition ensues and therapy that augments host immunity may be advantageous. Other immunomodulatory agents including granulocyte-macrophage colony-stimulating factor have shown promise in small trials in sepsis. ⋯ Animal studies show that these new immunoadjuvant agents improve survival in several clinically relevant models of sepsis. Given the relative safety of thymosin alpha-1 and these other new immunomodulatory agents as well as the persisting high mortality of sepsis, a strong case can be made for larger well-designed trials using immunoadjuvant therapy in patients who have documented immune suppression. Immunotherapy offers new hope in the treatment of sepsis and may dramatically change the face of the disease.
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One of the rationales for the use of vasopressin in septic shock has been its potential cardioprotective mechanisms. Lower heart rates, higher arterial pressures, and fewer norepinephrine doses during vasopressin therapy were hypothesized to protect the heart from myocardial ischemia. In a prospective sub-study of the VASST (Vasopressin in Septic Shock Trial) project, Mehta and colleagues specifically evaluated this hypothesis but failed to find lower cardiac biomarkers or fewer ischemic electrocardiogram changes in patients receiving vasopressin compared with subjects receiving norepinephrine alone. After recent evidence of a lacking survival benefit, the present study results further challenge the future role of vasopressin as a vasopressor in septic shock.
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Editorial Comment
Of ions and temperature: the complicated interplay of temperature, fluids, and electrolytes on myocardial function.
This article discusses the potential of levosimendan to treat calcium-induced myocardial dysfunction associated with deep hypothermia. Moderate hypothermia (30 to 34°C) usually improves myocardial contractility and stabilizes heart rhythm, but deep hypothermia can cause severe myocardial dysfunction, which is mediated by intracellular calcium overload. In experimental studies, levosimendan appears effective in reversing this. Clinical studies are needed to confirm these findings and to determine whether levosimendan could also be used for accidental hypothermia and perhaps to mitigate diastolic dysfunction under moderate hypothermia.