Juan J. Ronco

Intensive versus conventional glucose control in critically ill patients

BACKGROUND The optimal target range for blood glucose in critically ill patients remains unclear. METHODS Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)

Severity of illness and risk of death associated with pulmonary artery catheter use

ObjectiveTo examine the association between the use of the pulmonary artery catheter and mortality rate in critically ill patients with a higher vs. a lower severity of illness. DesignObservational cohort study. SettingA tertiary care university teaching hospital from March 1988 to March 1998. PatientsA total of 7,310 critically ill adult patients. InterventionsNone. Measurements and Main ResultsThe main outcome measure was hospital mortality rate, controlled by multivariable logistic regression within four patient groups based on severity of illness. Cutoffs for severity of illness were chosen based on Acute Physiology and Chronic Health Evaluation (APACHE) II score 25th percentiles. Logistic regression analysis demonstrated no increased risk of death associated with exposure to the pulmonary artery catheter in the population as a whole. The associated odds ratio of hospital death for the entire cohort was 1.05 (95% confidence interval, 0.92–1.21). Subgroup analysis of severity of illness revealed the highest risk of death to be associated with the lowest APACHE II score quartile vs. a decreased associated mortality rate with the highest APACHE II score quartile after adjustment with multivariable logistic regression (APACHE II <18: odds ratio, 2.47, 95% confidence interval, 1.27–4.81; APACHE II 18–24: odds ratio, 1.64, 95% confidence interval, 1.24–2.17; APACHE II 25–31: odds ratio, 1.00, 95% confidence interval, 0.80–1.24; APACHE II >31: odds ratio, 0.80, 95% confidence interval, 0.64–1.00). ConclusionsThe use of the pulmonary artery catheter may decrease mortality rate in the most severely ill while increasing it in a population with a lower severity of illness. These findings underscore the necessity of examining the effect of severity of illness in future randomized controlled trials.

Increased concentrations of plasma lactate predict pathologic dependence of oxygen consumption on oxygen delivery in patients with adult respiratory distress syndrome

Abstract We asked whether increasing systemic oxygen delivery by blood transfusion could identify pathologic dependence of oxygen consumption on oxygen delivery in patients who have adult respiratory distress syndrome (ARDS) with and without increased concentrations of plasma lactate. Twenty-four ARDS patients were divided into normal (n = 11, lactate ≤ 1.8 mmol/L) and increased (n = 13, lactate > 1.8 mmol/L) plasma lactate groups. After transfusion of two units of packed red blood cells, oxygen delivery index increased significantly in both the normal and increased plasma lactate groups. In the increased plasma lactate group, this was associated with a significant increase in oxygen consumption index and an unchanged oxygen extraction ratio. In contrast, in the normal plasma lactate group, oxygen consumption index did not change from the baseline value and the oxygen extraction ratio decreased significantly. We conclude that increasing systemic oxygen delivery by blood transfusion identifies pathologic dependence of oxygen consumption on oxygen delivery in patients who have ARDS and increased concentrations of plasma lactate.

Validation of an indirect calorimeter to measure oxygen consumption in critically ill patients

Abstract We tested a system of indirect calorimetry (Deltatrac Metabolic Monitor) for accuracy to measure oxygen consumption and sensitivity to detect small changes in oxygen consumption, in vitro, using a lung model simulation of ventilating patients who have stiff lungs. In vivo, we assessed reproducibility of the system to measure oxygen consumption in patients who had adult respiratory distress syndrome (ARDS) or sepsis. In vitro, oxygen consumptions of 100, 200, 300, and 500 mL/min were simulated by injecting N 2 into the lung model at 3-minute ventilations (10, 15, and 20 L/min) and at four levels of FIO 2 (0.40, 0.60, 0.70, and 0.80). After each baseline measurement, N 2 flow was increased to simulate an increase in VO 2 of 10% to 15%. At FIO 2 of 0.6 and 0.8, 15 cm H 2 O of positive end-expiratory pressure (PEEP) was applied to the lung model and measurements repeated. The Deltatrac had an average error of −2.1% (range, −7% to 3%). After simulated increases in oxygen consumption, the Deltatrac detected the change with an error less than 1% in all combinations tested. Although adding PEEP to the lung model altered accuracy of measurement, error was always less than 5%. We measured oxygen consumption in 27 ventilated and sedated patients who had severe ARDS or sepsis (FIO 2 , 0.60 ± 0.1; PEEP, 9 ± 3 cm H 2 O; static compliance, 27 ± 12 mL/cm H 2 O [mean ± SD]). Coefficient of variation for oxygen consumption was 4.6% ± 1.6%. Even at FIO 2 , 0.80 coefficient of variation was less than 6%. We conclude that this system of indirect calorimetry is accurate, sensitive, and reproducible to measure VO 2 in critically ill patients.

The impact of prolonged continuous wakefulness on resident clinical performance in the intensive care unit: a patient simulator study.

Objective:To evaluate the impact of prolonged continuous wakefulness on resident performance under controlled experimental conditions. Design:Experimental within-subjects comparison. Setting:High-fidelity patient simulator. Participants:Twelve residents in an Internal Medicine Program at various stages of training (range, 1–35 mos). Measurements:Performance was studied during 26 hrs of continuous wakefulness at four time points (8:00–10:00 am, 2:00–4:00 pm, 2:00–4:00 am, and 8:00–10:00 am the next day) using high-fidelity patient simulation. At each session, residents managed eight simulated dysrhythmias according to advanced cardiac life support protocols (advanced cardiac life support scenarios) and then managed a simulated critically ill patient (e.g., patient with meningitis) to test more complicated clinical decision-making (complex scenario). The frequency of previously defined major medical errors (i.e., action or inaction that likely would have resulted in significant harm in a real patient) was assessed by a scorer blinded to the time of the session. For each complex scenario, a global score between 0 and 100 was also given for overall performance. The impact of wakefulness on performance was assessed by using longitudinal mixed-effects models. Results:For the complex scenarios, the mean number of errors increased from 0.92 ± 0.90 in the first session to 1.58 ± 0.79 in the fourth session (p = .09), and mean global score decreased from 56.8 ± 14.6 to 49.6 ± 12.6 (p = .02). For the advanced cardiac life support scenarios, the mean number of major errors committed in the advanced cardiac life support scenarios decreased during the study period (p = .01). However, essentially all of the improvement occurred between the first and second time points, suggesting that a substantial learning effect accounted for the findings. Conclusions:During prolonged continuous wakefulness of medical residents, clinical performance in the management of a simulated critically ill patient deteriorates. The practice of scheduling residents for extended work shifts (>24 hrs) should be reconsidered.

Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study

IntroductionCritically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT.MethodsWe performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available.ResultsIn the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001).ConclusionsSOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution.

Intracranial pressure monitors in traumatic brain injury: a systematic review.

We conducted a systematic review to examine the relationship between intracranial pressure monitors (ICP) monitors and mortality in traumatic brain injury (TBI). We systematically searched for articles that met the following criteria: (1) adults patients, (2) TBI, (3) use of an ICP monitor, (4) point estimate for mortality with ICP monitoring (5) adjustment for potential confounders. Six observational studies were identified with 11,371 patients. There was marked between-study heterogeneity that precluded a pooled analysis. Patients with ICP monitors had different clinical characteristics and received more ICP targeted therapy in the ICU. Four studies found no significant relationship between ICP monitoring and survival, while the other two studies demonstrated conflicting results. Significant confounding by indication in observational studies limits the examination of isolated TBI interventions. More research should focus on interventions that affect TBI careplan systems. Further research is needed to identify which subset of severe TBI patients may benefit from ICP monitoring.

Blood transfusion as a cause of leucocytosis in critically ill patients

The diagnosis of infection in the intensive care unit is confounded by the presence of non-infectious causes of leucocytosis. Unless such causes are recognised, time and effort will be spent on unnecessary investigations and treatments. In a prospective study we have shown that the transfusion of blood frequently (45/50 patients) causes an acute leucocytosis in such patients. This effect was not seen in 8 patients who received plasma. Blood transfusion should be added to the list of non-infectious causes of leucocytosis in the critically ill.

Paralysis in the critically ill: intermittent bolus pancuronium compared with continuous infusion.

OBJECTIVES To compare recovery times from neuromuscular blockade between two groups of critically ill patients in whom pancuronium was administered by continuous infusion or intermittent bolus injection. To compare the mean pancuronium requirements (milligrams per kilogram per hour) and to assess the incidence of prolonged recovery times (>12 hrs) and residual muscle weakness. DESIGN Prospective, observational cohort. SETTING Intensive care unit in a university-affiliated hospital. PATIENTS A total of 30 mechanically ventilated patients who required pharmacologic paralysis. Patients were excluded if they had renal failure (creatinine clearance <30 mL/min), heart rate >130 beats/min, hepatic failure, peripheral nerve disease or myopathy, stroke, spinal cord damage, or myasthenia gravis. INTERVENTIONS Patients were assigned to receive pancuronium either by continuous infusion (n = 14) or intermittent bolus (n = 16). Depth of paralysis was titrated to maintain one or two responses to Train-of-Four stimulation with an accelerograph and desired clinical goals. Recovery time was defined as time from discontinuation of muscle relaxant until the amplitude of the fourth twitch, measured every 15-30 min using an accelerograph, was 70% the amplitude of the first twitch (Train-of-Four > or = 0.7). MEASUREMENTS AND MAIN RESULTS These patients included the only three patients with status asthmaticus in our study. The groups were similar with respect to age, sex, weight, Acute Physiology and Chronic Health Evaluation II score, mode of ventilation, creatinine clearance, indications for paralysis, and duration of pancuronium administration. The median time for patients to recover from paralysis was 3.5 hrs (95% confidence interval, 1.82-5.18) in the infusion group vs. 6.3 hrs (95% confidence interval, 3.40-9.19) in the intermittent bolus group (p = .10). Less drug was administered in the intermittent group (mean, 0.02+/-0.01 mg/kg/hr) than by infusion (mean, 0.04+/-0.01 mg/kg/hr; p < .001). Six patients (five in the infusion group and one in the intermittent group) developed persistent severe muscle weakness. In addition, six different patients (three from each group) had prolonged recovery >12 hrs. CONCLUSIONS Our study suggests that recovery time after paralysis with continuous infusion is faster than that after intermittent bolus injection. Although more pancuronium was administered in the continuous-infusion group, recovery time was not prolonged as a consequence. It is uncertain whether pancuronium given by infusion increases the risk of persistent muscle weakness.

Rapid Imipenem/Cilastatin Desensitization for Multidrug-Resistant Acinetobacter Pneumonia

OBJECTIVE: To report a successful case of rapid imipenem desensitization in a critically ill patient with multidrug-resistant Acinetobacter baumannii ventilator-associated pnemonia (VAP). CASE SUMMARY: A 40-year-old white man who had a lengthy stay in the intensive care unit (ICU) following a motorcycle accident developed VAP caused by A. baumannii. Treatment with imipenem was necessary due to the bacterias resistance to all other antibiotics. However, this patient was diagnosed with an allergy to imipenem following exposure earlier in his hospitalization in addition to a positive penicillin skin test. Thus, we attempted rapid desensitization to imipenem using a continuous infusion protocol. The patient was desensitized within 4 hours and was successfully treated for 21 days with a continuous infusion of imipenem combined with daily amikacin. He experienced no adverse reaction during the desensitization process or the remainder of his treatment course. DISCUSSION: The protocol used in this case was modified from a previously reported case, and differed in the speed of desensitization and total daily dose. We assumed that a more gradual escalation of the dose in our modified protocol would prevent the occurrence of adverse events, thereby resulting in more rapid desensitization. Rapid desensitization was necessary in this patient due to the presence of a life-threatening infection. The lower total daily dose of imipenem was in response to impaired renal function. CONCLUSIONS: Therapeutic options for multidrug-resistant pneumonia in the ICU are significantly limited in the presence of imipenem allergy. An option of last resort is to desensitize the patient using a rapid administration protocol. Our modified rapid imipenem desensitization protocol was successful and allowed for effective treatment of life-threatening pneumonia.