Daily Interruption of Sedation with Physical and Occupational Therapy in Mechanically Ventilated Patients

Schweickert et al. studied effects of early physical and occupational therapy in mechanically ventilated patients. 109 mechanically ventilated medical ICU patients (with independent functional status prior to hospitalization) were randomized to receive physical and occupational therapy initiated at time of enrollment (intervention group) vs. physical and occupational therapy ordered at the discretion of the primary team (control group), with both groups receiving daily interruptions of sedation. The primary outcome, independent functional status at time of discharge, was met in 59% of the intervention group vs. 35% of the control group (p = 0.02). Lower rates of ICU and hospital delirium were observed in the intervention group. Hospital length of stay and mortality were unaffected. This study demonstrated that physical and occupational therapy can be safely accomplished in critically ill, mechanically ventilated medical ICU patients, and that early implementation of therapy may improve return to independent functional status at hospital discharge.

Hydrocortisone Therapy for Patients with Septic Shock

This chapter provides a summary of the landmark study known as the CORTICUS trial. Among patients suffering from septic shock, does low dose hydrocortisone improve mortality? Starting with that question, it describes the basics of the study, including funding, study location, the population studies, number of patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The CORTICUS trial failed to demonstrate a benefit on mortality with steroid therapy among patients with septic shock. Based on CORTICUS and other studies, the Surviving Sepsis Campaign guidelines no longer recommend steroids for all patients with septic shock. Corticosteroids should be considered, however, for patients with septic shock who do not respond to fluids and vasopressor therapy.

Use of Procalcitonin to Reduce Patients’ Exposure to Antibiotics in Intensive Care Units (PRORATA Trial)

This chapter provides a summary of the landmark study known as the PRORATA trial. Does a procalcitonin (PCT)-based strategy to treat suspected bacterial infections in ICU patients reduce antibiotic exposure without adverse outcomes? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The study suggests that critically ill patients managed with a PCT-guided antibiotic strategy to treat suspected bacterial infections results in more antibiotic-free days than those managing patients with clinical guidelines alone. The mortality of patients in the PCT arm was non-inferior to those in the control group at day 28 and at day 60. The strategy could be beneficial for reducing antibiotic resistance in the ICU.

Comparison of 8 versus 15 Days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults

This chapter provides a summary of the landmark study “Comparison of 8 versus 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.” In adult patients with ventilator-associated pneumonia (VAP), is treatment with an 8-day course of antimicrobials as effective as a 15-day course? Starting with that question, the chapter describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. In ICU patients who develop microbiologically proven VAP, an 8-day antimicrobial course is not inferior to a 15-day course with respect to all-cause mortality or recurrence of pulmonary infection. However, these findings may not apply to patients who are immunocompromised, and shorter or longer duration of antibiotics may sometimes be indicated.

Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury

Patients with severe acute kidney injury who require renal replacement therapy have high mortality rates. Controversy exists over whether a mortality benefit occurs with use of a more intensive renal replacement therapy regimen. In this multicenter, prospective study, 1124 patients requiring renal replacement therapy for severe acute kidney injury were randomized to a more and a less intensive renal replacement therapy regimen and were followed for 60 days. There was no statistical difference in mortality at 60 days (53.6% intensive, 51.5% less intensive, P = 0.47) and no difference in kidney recovery or non-renal organ failure. Hypotension and electrolyte abnormalities were more common in the intensive renal replacement regimen. A less intensive renal replacement regimen (intermittent hemodialysis 3 times a week or continuous venovenous hemodiafiltration at 20ml/kg/hour) was found noninferior to a more intensive renal replacement strategy (dialysis 6 times per week or continuous venovenous hemodiafiltration at 35 ml/kg/hour).

Early versus On-Demand Nasoenteric Tube Feeding in Acute Pancreatitis

This study evaluated whether starting nasojejunal tube feeding within 24 hours of presentation would reduce the rate of death or major complications in patients with acute pancreatitis. This strategy was compared to allowing patients to take an “on demand” oral diet and only initiating nasojejunal tube feeding if there was poor oral intake by 96 hours after presentation. There was no difference between the two groups in any of the measured outcomes, though the study may have been underpowered. We conclude it is acceptable to allow an on-demand oral diet and reserve nasoenteric feeding for patients who have not achieved adequate nutrition by 96 hours after presentation. It is not necessary or beneficial to start nasojejunal tube feeds in the first 24 hours.

Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis

This chapter provides a summary of the landmark study known as the PROWESS Study. Does treatment with DAA reduce the rate of death from any cause among patients with severe sepsis? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The PROWESS trial demonstrated a mortality benefit for DAA among patients with severe sepsis. However, the subsequent ADDRESS, RESOLVE, and PROWESS-SHOCK trials did not demonstrate a benefit of the medication, thus calling the results of PROWESS into question.

Transfusion of plasma, platelets, and Red Blood Cells in a 1:1:1 versus a 1:1:2 Ration and Mortality in Patients with Severe Trauma

This chapter provides a summary of the landmark study known as the PROPPR trial. How effective and safe is rapid transfusion of patients with severe traumatic hemorrhage using plasma, platelets, and red blood cells in a 1:1:1 ratio compared to a 1:1:2 ratio? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. A growing body of literature suggests that massive transfusion protocols confer mortality benefits for trauma patients in hemorrhagic shock; however, such protocols still require standardization. In the PROPPR trial, there was suggestion of improved hemostasis and less death from exsanguinations with a 1:1:1 transfusion ratio versus a 1:1:2 approach; however, further trials are warranted.

A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care

This chapter provides a summary of the landmark study known as the TRICC trial. Is a restrictive strategy of red-cell transfusion equivalent to a liberal transfusion strategy in critically ill patients? Starting with that question, the chapter describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism, and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. Although this first large trial to examine the impact of transfusion thresholds on mortality in critically ill patients was underpowered, the trend toward decreased mortality in the restrictive group suggests that it is unlikely that the lower transfusion threshold subjects patients to increased harm. However, care must be taken in generalizing these results to cardiac surgery patients or to actively bleeding patients based on this study alone.

Early versus Late Parenteral Nutrition in the ICU

The EPaNIC study enrolled 4,640 critically ill adults who were nutritionally at risk and randomized them to either early (ICU day 3) or late (ICU day 8) supplemental parenteral nutrition (PN). In this study involving relatively thin patients with short ICU stays who were receiving tight glycemic control, early PN did not result in lower rates of mortality vs. late PN despite delivering significantly more calories in the first ICU week. In fact, late initiation of PN was associated with shorter duration of mechanical ventilation, lower incidence of renal replacement therapy, lower incidence of infections, and shorter ICU and hospital length of stay. Features of this study limiting external validity: most subjects had BMI 20–30, over 60% of subjects were post-cardiac surgery, overall median ICU stay was only 3 days, overall mortality was only 6%, nutritional management after ICU discharge was not controlled.