Critical care medicine traces its origins to the Crimean War of the 1850s, when Florence Nightingale designated a separate treatment space for the most severely wounded soldiers.1 At this point, the emphasis was on proximity to the nursing station and a higher level of nursing care. In 1923, Dr. Walter Dandy, a student of Harvey Cushing, created one of the first surgical intensive care units when he grouped his postoperative neurosurgical patients together in the same treatment area at Johns Hopkins.2 The original emphasis on intensive nursing care continued into World War II, with the development of “shock units” for care of the severely wounded.1
As medicine evolved, so did critical care. With the advent of organ system support devices, intensive nursing units transitioned into intensive therapy units. In the 1940s, iron lung wards (supplemented, where necessary, by medical students providing round-the-clock manual ventilation) supported patients with respiratory paralysis from polio. In the 1950s, hantavirus became a major cause of renal failure in Korean War soldiers, leading to the development of the first hemodialysis units. Concurrently, electrical defibrillators and transvenous cardiac pacing allowed the creation of specialized cardiac care units.1 In the 1960s, the creation of positive-pressure machines was a crucial step in the transition from iron lung wards to ventilatory care units.3
The isolated support of individual systems began to merge into true, multiorgan system support with the advent of improved vital sign monitoring, point-of-care analyzers, and STAT labs. This was supplemented by organizational restructuring, creating closed units and specialization for physicians and nurses.2 With the structure in place, major advances in treatment became possible. In particular, with critical care units in hospitals throughout the world, multicenter clinical research groups developed. These groups allowed for larger sample sizes, higher statistical power, and more rigorous and generalizable studies.4
Many of these studies are described in detail in the following chapter. They include the ARDSNet group in the United States, who in the 1990s and early 2000s demonstrated the benefit of low-tidal-volume ventilation for ARDS.5 In Canada, the Canadian Critical Care Trials Group demonstrated a mortality benefit to restrictive transfusion requirements that dramatically changed standard of care and resource utilization internationally.6 When single-center studies called into question the standard of care, as with early goal-directed therapy in the Rivers Trial,7 multicenter groups quickly formed to confirm or contest the results.8
Today, critical care units represent an increasing percentage of hospital beds, and that percentage is likely to continue to rise in the next few decades.9 Although trauma and burn surgeons dedicate their practices to critical care, surgeons in all specialties will be increasingly called on to care for patients with septic shock, hemorrhagic shock, and multiorgan system failure. Surgeons must remain informed as critical care evolves; evidence may prove common practices in the multidisciplinary, highly monitored units of today to be as outdated as the iron lung wards of yesterday.
A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation.
Yang KL, Tobin MJ
NEJM. 1991;324(21):1445–1450.Takeaway Point: The rapid shallow breathing index (RSBI), calculated as the ratio of respiratory frequency to tidal volume, predicts success of weaning from mechanical ventilation when < 105, and failure when > 105.
Commentary: The authors evaluate two new predictive indices of success at weaning from mechanical ventilation. Overall, the ratio of respiratory frequency to tidal volume, or rapid shallow breathing index (RSBI), was the best predictor of weaning success. The authors determined that a cutoff point of 105 yields the highest positive and negative predictive values. In a subsequent addendum, the authors calculated likelihood ratios for RSBI as a range, rather than an absolute cutoff. They concluded that RSBI < 80 is strongly predictive of weaning success, >100 is strongly predictive of failure, and 80–100 is a borderline group. The advantages of RSBI include ease of measurement and a simple calculation for use in the clinical setting.
Introduction: Predictive indices can assist in determining safe weaning from mechanical ventilation. Traditional parameters, including minute ventilation and vital capacity, have variable predictive value. The authors proposed two new indices: rapid shallow breathing index (RSBI), a ratio of respiratory frequency to tidal volume, and the CROP index, calculated from compliance, respiratory rate, oxygenation, and maximum inspiratory pressure.
Objectives: To evaluate the predictive power of two new indices to determine readiness to wean from a ventilator.
Trial Design: Single-center, prospective cohort study.
Inclusion Criteria: On ventilator support in the medical ICU and deemed appropriate for a weaning trial by their ICU physician.
Exclusion Criteria: Surgical patients.
Intervention: The first 36 patients enrolled constituted a “training set” to calculate a threshold value for each index that best differentiated patients who failed versus those who successfully weaned. The predictive power of the chosen threshold value was then tested prospectively in the next 64 patients enrolled.
Endpoints: The primary endpoint was successful weaning, defined as sustaining spontaneous breathing for >24 hours after extubation.
Sample Size: 100 patients at a single academic institution.
Statistical Analysis: Sensitivity and specificity, positive and negative predictive values, receiver-operating-characteristic (ROC) curves.
Baseline Data: 100 patients were evaluated, 46 men and 54 women. Average length of ventilator support 8.2 ±1.1 days. 60 patients were successfully weaned. 40 patients required reintubation within 24 hours for either clinical or laboratory parameters.
Outcomes: The threshold values that best discriminated between successful and unsuccessful trails of weaning were calculated. For the RSBI, a ratio of ≤105 had a sensitivity of 0.97, specificity of 0.64, positive predictive value (PPV) of 0.78, and negative predictive value (NPV) of 0.95. Overall, RSBI performed better than the CROP index or isolated respiratory parameters. Area under the ROC curve for RSBI was 0.89, significantly higher than other predictors.
Conclusion: The predictive powers of both proposed indices are better than traditional metrics. The RSBI has the highest predictive value and is easier to calculate.
Limitations: The trial included only medical patients. Definition of weaning failure included both clinical deterioration and abnormal lab values, and the difference was not explored. PPV and NPV depend on pretest probability, while likelihood ratios are independent of pretest probability and a better assessment of a predictive index. Additionally, a single cutoff point (105) has limited real-world applicability. After a letter to the editor from Jaeschke and Guyatt10 making these points, the authors presented likelihood ratios for weaning success: for RSBI <80, LR 7.5; 80–100 LR 0.77; and >100 LR 0.04.
A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care.
Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E, Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group
NEJM. 1999;340(6):409–417.Takeaway Point: In critically ill patients, transfusing for hemoglobin (Hgb) <7.0 is associated with improved survival compared with transfusing for hemoglobin <10.0.
Commentary: Prior to this trial, critically ill patients were routinely transfused to a goal Hgb of >10.0 g/dL (grams per deciliter). The authors performed a randomized parallel groups trial comparing liberal transfusion guidelines of Hgb>10 with a restrictive guideline recommending goal Hgb of 7.0–9.0. The restrictive group had a trend toward improved 30-day mortality, although the difference was not significant. The restrictive group had a 54% decrease in blood product utilization. The authors demonstrate that a restrictive transfusion guideline with a goal Hgb of 7.0–9.0 is at least equivalent, and possibly superior, to the liberal transfusion strategy. Although these results have been widely applied to many patient populations, it is worth remembering that the study population included only critically ill patients, and excluded cardiac patients.
Introduction: Critically ill patients are at increased risk for the immunosuppressive and microcirculatory complications of blood transfusions. Because of the risks associated with anemia and decreased oxygen delivery, transfusion guidelines in the ICU often have a goal Hgb of >10.0 g/dL.
Objectives: To compare a red cell transfusion protocol for goal Hgb 7.0–9.0 g/dL to a strategy of 10.0–12.0 g/dL in euvolemic, critically ill patients.
Trial Design: Randomized, nonblinded, parallel group controlled trial.
Inclusion Criteria: Anticipated ICU stay >24 hours, Hgb <9.0 within 72 hours of admission to the ICU, euvolemic after initial treatment.
Exclusion criteria: Age <16 years, inability to receive blood products, active/ongoing blood loss, chronic anemia, brain death, admission after routine cardiac surgery.
Intervention: Restrictive transfusion guideline, with transfusions given when Hgb fell below 7.0 as opposed to below 10.0.
Primary Endpoint: 30-day all-cause mortality.
Secondary Endpoints: 60-day all-cause mortality, ICU and hospital stay mortality, 30-day survival time, organ failure scores, composite outcomes of death and organ dysfunction.
Sample Size: 838 patients enrolled (6451 screened) from 22 tertiary care centers and three community hospitals in Canada. 420 randomized to liberal group, 418 to restrictive group.
Statistical Analysis: Intention-to-treat analysis, Tukey’s honestly-significant-difference test for pairwise comparisons, Fisher’s exact test, logistic regression, Kaplan–Meier curves, χ2 test, Wilcoxon rank sum test.
Baseline Data: Baseline characteristics were balanced between the two groups. Most common reasons for ICU admission were respiratory and cardiac disease. Over 80% required intubation. 26.5% were admitted with infection.
Outcomes: Average daily Hgb in the liberal group was 10.7, with an average of 5.6 units transfused per patient. The restrictive group had an average daily Hgb of 8.5 and an average of 2.6 units transfused per patient (54% decrease in transfusions). 33% of restrictive patients received no transfusions; all patients in the liberal group received transfusions. The 30-day mortality for the restrictive group was 18.7%, compared with 23.3% in the liberal group (p 0.11). In-hospital mortality, ICU mortality, and 60-day mortality were lower in the restrictive group, although not significantly. Rates of cardiac complications were significantly lower in the restrictive group (13.2% vs. 21%, p <0.01).
Conclusion: The use of a restrictive threshold for red cell transfusion, with a goal Hgb of 7.0–9.0, is equivalent or superior to a more liberal goal of 10.0–12.0 g/dL.
Limitations: The study did not include cardiac surgery patients, and study results cannot be generalized to that population. Overall enrollment was significantly lower than expected, and only 13% of patients screened were enrolled in the study, raising concerns for external validity.
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.
Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A, for the Acute Respiratory Distress Syndrome Network
NEJM. 2000;342(18):1301–1308.Takeaway Point: In critically ill patients with acute respiratory distress syndrome (ARDS), a ventilation strategy using tidal volumes of 6 cm3/kg is associated with lower mortality and greater number of ventilator-free days when compared with 12 cm3/kg tidal volumes.
Commentary: The authors presented a large, multi-institution randomized controlled trial comparing traditional tidal volumes of 12 cm3/kg with a low tidal volume of 6 cm3/kg for patients with ARDS. The trial was stopped early when an interim analysis showed a clear mortality benefit in the lower tidal volume group. The trial has been criticized for using 12 cm3/kg as a standard tidal volume, when many centers at that time used an intermediate goal of 10 cm3/kg. Additionally, the lower tidal volume group had higher average positive end-expiratory pressure (PEEP) than did the control group, raising questions of whether PEEP or tidal volume contributed most to the beneficial effects. Overall, however, this trial demonstrated a significant benefit to lower tidal volume ventilation for patients with ARDS. Their findings have been validated by a Cochrane review in 2013, and have been incorporated into the Surviving Sepsis Campaign 2012 guidelines.
Introduction: ARDS is associated with atelectasis, edema, and fibrosis, and has traditionally been treated with high-tidal-volume ventilation to counteract respiratory acidosis and hypoxia. Animal trials, however, suggested worsening inflammation and barotrauma with this strategy.
Objectives: The present trial was conducted to determine whether the use of a lower tidal volume with mechanical ventilation would improve important clinical outcomes.
Trial Design: Multicenter randomized controlled trial.
Inclusion Criteria: Intubated on mechanical ventilation, diagnosis of ARDS [ratio of partial pressure of O2 to fraction of inspired oxygen <300, bilateral pulmonary infiltrates; no clinical evidence of left atrial (LA) hypertension, or pulmonary capillary wedge pressure (PCWP) <18].
Exclusion Criteria: >36 hours since meeting ARDS criteria, age <18 years, pregnant, increased intracranial pressure (ICP), neuromuscular disease, sickle cell disease, severe chronic respiratory disease, morbid obesity, burns >30% of body surface area (BSA), estimated 6-month mortality >50%, bone marrow or lung transplant, Child–Pugh class C liver disease.
Lower-Tidal-Volume Group: Tidal volume 6 cm3/kg predicted body weight, reduced by 1 cm3/kg to maintain plateau pressure <30, minimal tidal volume of 4 cm3/kg.
Control Group: Tidal volume 12 cm3/kg predicted body weight, decreased by 1 cm3/kg if necessary to maintain plateau pressure <50; minimum tidal volume 4 cm3/kg predicted body weight.
Primary Endpoint: Death prior to discharge home off the ventilator.
Secondary Endpoints: Ventilator-free days, organ system failure, time until barotrauma.
Sample Size: 861 patients were randomized, 432 to lower tidal volumes and 429 to traditional, at 10 university centers from 1996 to 1999.
Statistical Analysis: Student’s t-test or Fisher’s exact, analysis of covariance, Wilcoxon’s test, χ2; planned interim analyses.
Baseline Data: Baseline characteristics were overall balanced between the two groups.
Primary: The lower-tidal-volume group had significantly lower tidal volumes and plateau pressures. Mortality at 180 days was 39.8% in the traditional tidal volume group, compared with 31% in the lower tidal volume group (p 0.007). The difference was sufficiently significant that the trial was stopped early.
Secondary: The lower-tidal-volume group had a significantly higher number of ventilator-free days (12 vs. 10, p 0.007), and organ-failure-free days. Incidence of barotrauma was similar in the two groups.
Conclusion: In patients with ARDS, ventilation with lower tidal volumes of 6 cm3/kg are associated with lower mortality at 180 days when compared with 12 cm3/kg tidal volumes.
Limitations: The two comparison groups may both have represented a departure from standard practice. Volumes of 12 cm3/kg are higher than standard, and the standardized PEEP strategy used in the trial resulted in higher average PEEP in the lower-tidal-volume group. Additionally, the majority of analyses in the trial were univariate comparisons of mean values. Causes of death were not reported. The trial was cited by OHRP for providing insignificant informed consent to participants.
Early goal-directed therapy in the treatment of severe sepsis and septic shock.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, for the Early Goal-Directed Therapy Collaborative Group
NEJM. 2001;345(19):1368–1377.Takeaway Point: Early goal-directed therapy for sepsis or septic shock reduces in-hospital, 30- and 60-day mortality.
Commentary: Goal-directed therapy for septic shock involves treatment targeted to cardiac preload, afterload, and contractility to balance oxygen delivery and oxygen demand. The authors targeted these goals within the “golden hours” between presentation with systemic inflammatory response syndrome (SIRS) and development of global tissue hypoxia. Prior studies enrolled patients within 72 hours of ICU admission; this trial targeted the first 6 hours after presentation to the emergency department. Of note, some components of early goal-directed therapy (EGDT) have come under controversy: specifically, transfusion goal hematocrit (Hct) of 30 contradicts the previously published TRICC Trial (see b, above), and use of CVP as surrogate for blood volume is not well established.11 The overall results of the trial, however, are compelling, with a 16% reduction to in-hospital mortality. These results were replicated in other centers12,13 but had not been evaluated in a multi-institution trial until 2014 (see j, below).
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