Impella CP Versus Intra-Aortic Balloon Pump in Acute Myocardial Infarction Complicated by Cardiogenic Shock: The IMPRESS trial.

This article by Ouweneel et al was published in the Journal of the American College of Cardiology.  Subscribers to the journal can access the full text of the article via this link.  The full text is available to those with an NHS Athens password via the Proquest website sixty days after publication.  Individual articles can be ordered via the Rotherham NHS Foundation Trust Library and Knowledge Service.  Registered members of the library can make article requests online via this link

Background: Despite advances in treatment, mortality in acute myocardial infarction complicated by cardiogenic shock remains high. Short-term mechanical circulatory support devices acutely improve hemodynamic conditions. The Impella CP is a new percutaneous circulatory support device that provides more hemodynamic support than the intra-aortic balloon pump (IABP).

Objectives: The aim of this study was to determine whether the Impella CP can decrease 30-day mortality when compared with IABP in patients with severe shock complicating acute myocardial infarction.

Methods:  In a randomized, prospective, open-label, multi-center trial, we assigned 48 patients with severe cardiogenic shock complicating acute myocardial infarction to Impella CP (n=24) or IABP (n=24). Severe cardiogenic shock was defined as systolic blood pressure lower than 90 mmHg or the need for inotropic or vasoactive medication and the requirement for mechanical ventilation. The primary endpoint was 30-day all-cause mortality.

Results:  At 30 days, mortality in patients treated with either IABP or Impella CP was similar (50% and 46%, respectively, hazard ratio (HR) with Impella CP, 0.96 (95% confidence interval (CI) 0.42 to 2.18; p=0.92). At 6 months, mortality rates for both Impella CP and IABP were 50% (HR 1.04 (95% CI; 0.47-2.32, p=0.923).

Conclusions:  In this explorative randomized controlled trial involving mechanically ventilated cardiogenic shock patients after acute myocardial infarction, routine treatment with Impella CP was not associated with reduced 30-day mortality compared with IABP.

Resting energy expenditure, calorie and protein consumption in critically ill patients

Zusman, O. et al. Critical Care. Published: 10 November 2016

Background: Intense debate exists regarding the optimal energy and protein intake for intensive care unit (ICU) patients. However, most studies use predictive equations, demonstrated to be inaccurate to target energy intake. We sought to examine the outcome of a large cohort of ICU patients in relation to the percent of administered calories divided by resting energy expenditure (% AdCal/REE) obtained by indirect calorimetry (IC) and to protein intake.

Methods: Included patients were hospitalized from 2003 to 2015 at a 16-bed ICU at a university affiliated, tertiary care hospital, and had IC measurement to assess caloric targets. Data were drawn from a computerized system and included the % AdCal/REE and protein intake and other variables. A Cox proportional hazards model for 60-day mortality was used, with the % AdCal/REE modeled to accommodate non-linearity. Length of stay (LOS) and length of ventilation (LOV) were also assessed.

Results: A total of 1171 patients were included. The % AdCal/REE had a significant non-linear (p < 0.01) association with mortality after adjusting for other variables (p < 0.01). Increasing the percentage from zero to 70 % resulted in a hazard ratio (HR) of 0.98 (CI 0.97–0.99) pointing to reduced mortality, while increases above 70 % suggested an increase in mortality with a HR of 1.01 (CI 1.01–1.02). Increasing protein intake was also associated with decreased mortality (HR 0.99, CI 0.98–0.99, p = 0.02). An AdCal/REE >70 % was associated with an increased LOS and LOV.

Conclusions: The findings of this study suggest that both underfeeding and overfeeding appear to be harmful to critically ill patients, such that achieving an Adcal/REE of 70 % had a survival advantage. A higher caloric intake may also be associated with harm in the form of increased LOS and LOV. The optimal way to define caloric goals therefore requires an exact estimate, which is ideally performed using indirect calorimetry. These findings may provide a basis for future randomized controlled trials comparing specific nutritional regimens based on indirect calorimetry measurements.

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Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial

This randomised controlled trial by Keh et al for SepNet–Critical Care Trials Group was published in JAMA in November 2016 (JAMA. 2016;316(17):1775-1785).  The full text of the article is available to subscribers via this link.  Registered members of the library can request the full text online via this link.

Importance:  Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial.

Objective:  To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.  Design, Setting, and Participants: Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock.

Interventions:  Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190).

Main Outcomes and Measures:  The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]).

Results:  The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, −1.8%; 95% CI, −10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, −5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, −5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, −4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia.

Conclusions and Relevance:  Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients.

Clinical Review: Paracetamol in fever in critically ill patients – an update

Chiumello, D. et al. Journal of Critical Care. Published online: November 4, 2016


Fever, that is arbitrary defined as an increase in body temperature above 38.3 °C, can affect up to 90% of patients admitted in intensive care unit. Induction of fever is mediated by the release of pyrogenic cytokines (tumor necrosis factor alfa, interleukin-1, interleukin-6 and interferons). Fever is associated with increased length of stay in intensive care unit and with a worse outcome in some subgroups of patients (mainly neurocritically ill patients).

Although fever can increase oxygen consumption in unstable patients on the contrary can activate physiologic systems that are involved in pathogens clearance. Treatments to reduce fever include the use of antipyretics. Thus the reduction of fever might reduce the ability to develop an efficient host response. This balance, between harms and benefits, has to be taken into account every time we decide to treat or not to treat fever in a given patient.

Treatments to reduce fever include the use of antipyretics. Among the antipyretics Paracetamol is one of the most common used. Paracetamol is a synthetic, nonopioid, centrally acting analgesic and antipyretic drug. Its antipyretic effect occurres because it inhibits cyclooxygenase-3 and the prostaglandin synthesis, within the central nervous system, resetting the hypothalamic heat-regulation center. In this clinical review we will summarize the use of Paracetamol as antipyretic in critically ill patients (sepsis, trauma, neurological and medical).

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Lower versus higher dose of enteral caloric intake in adult critically ill patients: a systematic review and meta-analysis

Al-Dorzi, H. M. et al. Critical Care. Published online: 4 November 2016

Background: There is conflicting evidence about the relationship between the dose of enteral caloric intake and survival in critically ill patients. The objective of this systematic review and meta-analysis is to compare the effect of lower versus higher dose of enteral caloric intake in adult critically ill patients on outcome.

Methods: We reviewed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from inception through November 2015. We included randomized and quasi-randomized studies in which there was a significant difference in the caloric intake in adult critically ill patients, including trials in which caloric restriction was the primary intervention (caloric restriction trials) and those with other interventions (non-caloric restriction trials). Two reviewers independently extracted data on study characteristics, caloric intake, and outcomes with hospital mortality being the primary outcome.

Results: Twenty-one trials mostly with moderate bias risk were included (2365 patients in the lower caloric intake group and 2352 patients in the higher caloric group). Lower compared with higher caloric intake was not associated with difference in hospital mortality (risk ratio (RR) 0.953; 95 % confidence interval (CI) 0.838–1.083), ICU mortality (RR 0.885; 95 % CI 0.751–1.042), total nosocomial infections (RR 0.982; 95 % CI 0.878–1.077), mechanical ventilation duration, or length of ICU or hospital stay. Blood stream infections (11 trials; RR 0.718; 95 % CI 0.519–0.994) and incident renal replacement therapy (five trials; RR 0.711; 95 % CI 0.545–0.928) were lower with lower caloric intake. The associations between lower compared with higher caloric intake and primary and secondary outcomes, including pneumonia, were not different between caloric restriction and non-caloric restriction trials, except for the hospital stay which was longer with lower caloric intake in the caloric restriction trials.

Conclusions: We found no association between the dose of caloric intake in adult critically ill patients and hospital mortality. Lower caloric intake was associated with lower risk of blood stream infections and incident renal replacement therapy (five trials only). The heterogeneity in the design, feeding route and timing and caloric dose among the included trials could limit our interpretation. Further studies are needed to clarify our findings.

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Advanced extracorporeal therapy in trauma

Zonies, D. & Merkel, M.Current Opinion in Critical Care22(6) pp. 578–583

Purpose of review: The purpose is to review the current application of extracorporeal life support (ECLS) in trauma patients. In addition, programmatic development is described.

Recent findings: ECLS use is increasing among trauma patients. Several recent studies among trauma patients report survival rates of 65–79%. Despite the high bleeding risk, extracorporeal membrane oxygenation (ECMO) may be safely implemented in trauma patients based on a strict protocol-driven policy. Early implementation may improve overall outcomes. Alternative anticoagulants and heparin free periods may be well tolerated in trauma patients at high risk of hemorrhage.

Summary: ECMO is becoming a more routine option in severely injured trauma patients that develop severe respiratory failure. Well tolerated implementation and program development is possible among regional trauma centers. Although clinical knowledge gaps exist, ECMO is a promising treatment in this high-risk population.

Cytomegalovirus infection in immunocompetent critically ill adults: literature review

Al-Omari, A. et al. (2016) Annals of Intensive Care. 6:110
Image source: Pete Jeffs – Wellcome Images // CC BY-NC-ND 4.0

Image shows artist’s interpretation of a human cytomegalovirus virion based on cryo-electron microscopy images

Cytomegalovirus (CMV) infection is increasingly recognized in critically ill immunocompetent patients.

Some studies have demonstrated an association between CMV disease and increased mortality rates, prolonged intensive care unit and hospital length of stay, prolonged mechanical ventilation, and nosocomial infections. However, there is a considerable controversy whether such association represents a causal relationship between CMV disease and unfavorable outcomes or just a marker of the severity of the critical illness.

Detection of CMV using polymerase chain reaction and CMV antigenemia is the standard diagnostic approach. CMV may have variety of clinical manifestations reflecting the involvement of different organ systems. Treatment of CMV in critical care is challenging due to diagnostic challenge and drug toxicity, and building predictive model for CMV disease in critical care setting would be promising to identify patients at risk and starting prophylactic therapy.

Our objective was to broadly review the current literature on the prevalence and incidence, clinical manifestations, potential limitations of different diagnostic modalities, prognosis, and therapeutic options of CMV disease in critically ill patients.

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VANISH: a challenge for current sepsis guidelines!

Rehberg, S. et al. Critical Care. Published online: 31 October 2016

Haemodynamic therapy in septic shock with non-adrenergic compounds such as the vasopressin-receptor agonist arginine vasopressin (AVP) , the calcium-sensitizer levosimendan , or beta-blockers is gaining more and more attention since the potential negative effects of catecholamines in shock are well recognized. The VANISH trial focused on the effects of AVP versus norepinephrine on renal failure (as the primary outcome) and mortality rates at 28 days and serious adverse events (as secondary outcomes). Although there might have been a potential benefit on kidney-failure-free days, overall the trial revealed no statistically significant differences regarding these outcomes. Thus, just another negative, randomised controlled trial in sepsis? Not at all!

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