Background Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. Methods We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter and maintenance of glucose at a level between 180 and 200 mg per deciliter). Results At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa011300

Intensive Insulin Therapy in Critically Ill Patients

A b s t r ac t Background The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. Methods In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer’s lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. Results The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, ≤40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P = 0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer’s lactate. Conclusions The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials. gov number, NCT00135473.)

/pdf/intensive-insulin-therapy-and-pentastarch-resuscitation-in-386eht3k3e.pdf

Intensive insulin therapy and pentastarch resuscitation in severe sepsis.

ContextEvaluation of trends in organ dysfunction in critically ill patients
may help predict outcome.ObjectiveTo determine the usefulness of repeated measurement the Sequential Organ
Failure Assessment (SOFA) score for prediction of mortality in intensive care
unit (ICU) patients.DesignProspective, observational cohort study conducted from April 1 to July
31, 1999.SettingA 31-bed medicosurgical ICU at a university hospital in Belgium.PatientsThree hundred fifty-two consecutive patients (mean age, 59 years) admitted
to the ICU for more than 24 hours for whom the SOFA score was calculated on
admission and every 48 hours until discharge.Main Outcome MeasuresInitial SOFA score (0-24), Δ-SOFA scores (differences between
subsequent scores), and the highest and mean SOFA scores obtained during the
ICU stay and their correlations with mortality.ResultsThe initial, highest, and mean SOFA scores correlated well with mortality.
Initial and highest scores of more than 11 or mean scores of more than 5 corresponded
to mortality of more than 80%. The predictive value of the mean score was
independent of the length of ICU stay. In univariate analysis, mean and highest
SOFA scores had the strongest correlation with mortality, followed by Δ-SOFA
and initial SOFA scores. The area under the receiver operating characteristic
curve was largest for highest scores (0.90; SE, 0.02; P<.001 vs initial score). When analyzing trends in the SOFA score
during the first 96 hours, regardless of the initial score, the mortality
rate was at least 50% when the score increased, 27% to 35% when it remained
unchanged, and less than 27% when it decreased. Differences in mortality were
better predicted in the first 48 hours than in the subsequent 48 hours. There
was no significant difference in the length of stay among these groups. Except
for initial scores of more than 11 (mortality rate >90%), a decreasing score
during the first 48 hours was associated with a mortality rate of less than
6%, while an unchanged or increasing score was associated with a mortality
rate of 37% when the initial score was 2 to 7 and 60% when the initial score
was 8 to 11.ConclusionsSequential assessment of organ dysfunction during the first few days
of ICU admission is a good indicator of prognosis. Both the mean and highest
SOFA scores are particularly useful predictors of outcome. Independent of
the initial score, an increase in SOFA score during the first 48 hours in
the ICU predicts a mortality rate of at least 50%.

https://jamanetwork.com/journals/jama/articlepdf/194262/JCE00056.pdf

Serial evaluation of the SOFA score to predict outcome in critically ill patients.

Acute kidney injury

ContextThe outcome of patients receiving mechanical ventilation for particular
indications has been studied, but the outcome in a large number of unselected,
heterogeneous patients has not been reported.ObjectiveTo determine the survival of patients receiving mechanical ventilation
and the relative importance of factors influencing survival.Design, Setting, and SubjectsProspective cohort of consecutive adult patients admitted to 361 intensive
care units who received mechanical ventilation for more than 12 hours between
March 1, 1998, and March 31, 1998. Data were collected on each patient at
initiation of mechanical ventilation and daily throughout the course of mechanical
ventilation for up to 28 days.Main Outcome MeasureAll-cause mortality during intensive care unit stay.ResultsOf the 15 757 patients admitted, a total of 5183 (33%) received
mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean
(SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall
mortality rate in the intensive care unit was 30.7% (1590 patients) for the
entire population, 52% (120) in patients who received ventilation because
of acute respiratory distress syndrome, and 22% (115) in patients who received
ventilation for an exacerbation of chronic obstructive pulmonary disease.
Survival of unselected patients receiving mechanical ventilation for more
than 12 hours was 69%. The main conditions independently associated with increased
mortality were (1) factors present at the start of mechanical ventilation
(odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR,
3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway
pressure >35 cm H2O), and (3) developments occurring over the course
of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO2 to fraction of inspired oxygen
<100).ConclusionSurvival among mechanically ventilated patients depends not only on
the factors present at the start of mechanical ventilation, but also on the
development of complications and patient management in the intensive care
unit.

https://jamanetwork.com/journals/jama/articlepdf/194560/JCE10020.pdf

Characteristics and Outcomes in Adult Patients Receiving Mechanical Ventilation: A 28-Day International Study

Background The administration of growth hormone can attenuate the catabolic response to injury, surgery, and sepsis. However, the effect of high doses of growth hormone on the length of stay in intensive care and in the hospital, the duration of mechanical ventilation, and the outcome in critically ill adults who are hospitalized for long periods is not known. Methods We carried out two prospective, multicenter, double-blind, randomized, placebo-controlled trials in parallel involving 247 Finnish patients and 285 patients in other European countries who had been in an intensive care unit for 5 to 7 days and who were expected to require intensive care for at least 10 days. The patients had had cardiac surgery, abdominal surgery, multiple trauma, or acute respiratory failure. The patients received either growth hormone (mean [±SD] daily dose, 0.10±0.02 mg per kilogram of body weight) or placebo until discharge from intensive care or for a maximum of 21 days. Results The in-hospital mortality rate was higher...

Increased mortality associated with growth hormone treatment in critically ill adults.

Objective: To evaluate the performance of total maximum sequential organ failure assessment (SOFA) score and a derived measure, delta SOFA (total maximum SOFA score minus admission total SOFA) as a descriptor of multiple organ dysfunction/failure in intensive care. Design: Prospective, multicentre and multinational study. Setting: Forty intensive care units (ICUs) from Australia, Europe, North and South America. Patients: Data on 1,449 patients, evaluated at admission and then consecutively every 24 h until ICU discharge (11,417 records) during May 1995. Excluded from data collection were all patients with a length of stay in the ICU less than 2 days following uncomplicated scheduled surgery. Main outcome measure: Survival status at ICU discharge. Interventions: The collection of raw data necessary for the computation of a SOFA score on admission and then every 24 h, and basic demographic and clinical statistics. Measurements and main results: Mean total maximum SOFA score presented a very good correlation to ICU outcome, with mortality rates ranging from 3.2 % in patients without organ failure to 91.3 % in patients with failure of all the six organs analysed. A maximum score was reached 1.1 ± 0.2 days after admission for all the organ systems analysed. The total maximum SOFA score presented an area under the ROC curve of 0.847 (SE 0.012), which was significantly higher than any of its individual components. The cardiovascular score (odds ratio 1.68) was associated with the highest relative contribution to outcome. No independent contribution could be demonstrated for the hepatic score. No significant interactions were found. Principal components analysis demonstrated the existence of a two-factor structure that became clearer when analysis was limited to the presence or absence of organ failure (SOFA score ≥ 3 points) during the ICU stay. The first factor comprises respiratory, cardiovascular and neurological systems and the second coagulation, hepatic and renal systems. Delta SOFA also presented a good correlation to outcome. The area under the receiver operating characteristic (ROC) curve was 0.742 (SE 0.017) for delta SOFA, lower than the total maximum SOFA score or admission total SOFA score. The impact of delta SOFA on prognosis remained significant after correction for admission total SOFA. Conclusions: The results show that total maximum SOFA score and delta SOFA can be used to quantify the degree of dysfunction/failure already present on ICU admission, the degree of dysfunction/failure that appears during the ICU stay and the cumulative insult suffered by the patient. These properties make it a good instrument to be used in the evaluation of organ dysfunction/failure.

The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study

Objective: To define the occurrence rate of acute respiratory distress syndrome (ARDS) using established criteria in a well-defined general patient population, to study the clinical course of ARDS when patients were ventilated using a lung-protective strategy, and to define the total costs of care. Design: A 3-yr (1993 through 1995) retrospective descriptive analysis of all patients with ARDS treated in Kuopio University Hospital. Setting: Intensive care unit in the university hospital. Patients: Fifty-nine patients fulfilled the definition of ARDS: Pao 2 /Fio 2 < 200 mm Hg (33.3 kPa) during mechanical ventilation and bilateral infiltrates on chest radiograph. interventions: None. Measurements and Main Results: With a patient data management system, the day-by-day data of hemodynamics, ventilation, respiratory mechanics, gas exchange, and organ failures were collected during the period that Pao 2 /Fio 2 ratio was <200 mm Hg (33.3 kPa). The frequency of ARDS was 4.9 cases/100,000 inhabitants/yr. Pneumonia and sepsis were the most common causes of ARDS. Mean age was 43 ± 2 yrs. At the time of lowest Pao 2 /Fio 2 , the nonsurvivors had lower arterial and venous oxygen saturations and higher arterial lactate than survivors, whereas there were no differences between the groups in other parameters. Multiple organ dysfunction preceded the worst oxygenation in both the survivors and nonsurvivors. The intensive care mortality was 37%; hospital mortality and mortality after a minimum 8 months of follow-up was 42%. The most frequent cause of death was multiple organ failure. The effective costs of intensive care per survivor were US $73,000. Conclusions: The outcome of ARDS is unpredictable at the time of onset and also at the time of the worst oxygenation. Keeping the inspiratory pressures low (30-35 cm H 2 O [2.94 to 3.43 kPa]) reduces the frequency of pneumothorax, and might lower the mortality. Most patients are young, and therefore the costs per saved year of life are low.

Acute respiratory distress syndrome: frequency, clinical course, and costs of care.

ObjectiveTo assess the subjective health status, quality of life, and functional ability of patients whose intensive care stay was prolonged and to compare their quality of life with that of the general population.DesignInception cohort study.SettingTwenty-three-bed multidisciplinary intensive care

Quality of life after prolonged intensive care.

To assess the usefulness of markers of inflammation in distinguishing bacterial infection from severe systemic nonbacterial inflammation, concentrations of procalcitonin, neopterin, endotoxin, tumor necrosis factor, and interleukin-6 were measured in 28 neutropenic patients at the onset of fever and twice thereafter at 4 h intervals. Infection was found in 11 patients, and 17 patients had fever of undetermined origin. The procalcitonin concentration increased rapidly in patients with infection; the response was detectable within 8 h of the onset of fever. Procalcitonin is a specific but not a sensitive marker of infection in patients with neutropenic fever. Its poor sensitivity was related to an absent or delayed response in patients with gram-positive infections. Considerable overlap between infected and noninfected patients was found in levels of endotoxin, tumor necrosis factor, and interleukin-6.

Jukka Takala

Papers

Increased mortality associated with growth hormone treatment in critically ill adults.

The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study

Acute respiratory distress syndrome: frequency, clinical course, and costs of care.

Quality of life after prolonged intensive care.

Procalcitonin concentrations in patients with neutropenic fever.