Prognosis for acutely ill patients with cirrhosis is in-hepatic portosystemic shunting 3-7 and other operative fluenced by the severity of hepatic abnormalities and by procedures. [8][9][10][11] These systems have also been useful for dysfunction of other organ systems. The purpose of this risk-stratifying groups of patients with cirrhosis, [12][13][14][15] in study was to examine the usefulness of the Acute Physi-evaluating therapy for complications of cirrhosis, [16][17][18] ology, Age, and Chronic Health Evaluation (APACHE III) and in assessing the efficacy of procedures such as prognostic system for risk-stratifying groups of inten-sclerotherapy. [19][20][21] Although useful for clinical trials, sive care unit (ICU) patients with cirrhosis and in pre-the Child-Pugh classification has limited predictive acdicting individual survival. We used data for 17,440 ICU curacy for individuals because of overlapping criteria, admissions at 40 American hospitals to select 117 of the and interobserver variation for subjective criteria. 3,22 537 patients with a history of cirrhosis who were ventiIn addition, important prognostic factors unrelated to lated on ICU day 1, a group known to have a high mortality rate. We then calculated each patient's probability of hepatic function, e.g., measures of renal function, 23,24 hospital death on ICU days 1 through 7, using seven arterial pressure, 25 and study entry time, 26 are not inpreviously validated multivariate equations. Hospital cluded. Because of these limitations, we examined the mortality was 63% for the 117 study patients. The most usefulness of APACHE III (Acute Physiology, Age, and important determinants of risk for hospital death on Chronic Health Evaluation), a physiologically based ICU day 1 were the acute physiology score of APACHE prognostic system, 27 in assessing prognosis for groups III, ICU admission diagnosis, and operative status. Daily of intensive care unit (ICU) admissions with cirrhosis. changes in the acute physiology score caused a rise or ICU admission for patients with cirrhosis has prefall in the probability of hospital mortality and was useviously been recognized to result in low survival ful in assessing individual response to therapy. APACHE III accurately risk stratifies critically ill patients with rates. [28][29][30][31] Poor outcomes are common for all ICU pacirrhosis because it accounts for many of the factors tients with multiple organ system dysfunction or failknown to influence prognosis. This capability can be ure, 32-34 but survival is particularly poor among individused to assess severity of illness and risk-stratify pa-uals with cirrhosis who develop extrahepatic organ tients with cirrhosis during clinical trials. Daily prog-system failure. [35][36][37][38][39][40] For example, hospital mortality nostic estimates based on physiological changes over ranged from 89% to 95% in three studies involving 220 time reflect patient response and can help physicians to nonoperative ICU admissions with cirrhosis who also poor outcome results, we...

How mammalian neural circuits generate rhythmic activity in motor behaviors, such as breathing, walking, and chewing, remains elusive. For breathing, rhythm generation is localized to a brainstem nucleus, the preBötzinger Complex (preBötC). Rhythmic preBötC population activity consists of strong inspiratory bursts, which drive motoneuronal activity, and weaker burstlets, which we hypothesize reflect an emergent rhythmogenic process. If burstlets underlie inspiratory rhythmogenesis, respiratory depressants, such as opioids, should reduce burstlet frequency. Indeed, in medullary slices from neonatal mice, the μ-opioid receptor (μOR) agonist DAMGO slowed burstlet generation. Genetic deletion of μORs in a glutamatergic preBötC subpopulation abolished opioid-mediated depression, and the neuropeptide Substance P, but not blockade of inhibitory synaptic transmission, reduced opioidergic effects. We conclude that inspiratory rhythmogenesis is an emergent process, modulated by opioids, that does not rely on strong bursts of activity associated with motor output. These findings also point to strategies for ameliorating opioid-induced depression of breathing.

Organ system failure remains a major contributor to death in patients in ICUs. The incidence and overall outcome have not significantly changed over the past 8 yrs, but there has been significant improvement in survival for patients with persistent severe organ system failure. A continuous measure of individual patient severity of illness is a more sensitive and accurate method for describing patients and estimating outcome than counting the number of organ system failures.

We conducted a cohort study of 423 intensive care unit (ICU) admissions with a primary clinical diagnosis of acute respiratory failure, a PaO2/FIO2 on ICU admission of < 300 mm Hg, and an ICD-9 discharge diagnosis of adult respiratory distress syndrome (ARDS) (518.5 or 518.82) drawn from a nationally representative database of 17,440 ICU admissions to evaluate current and proposed revisions for definitions of ARDS. A variety of nonpulmonary physiologic risk factors, from shock to elevated serum bilirubin measurements, were significant (p < 0.01) for hospital mortality. Multivariable analysis using the admission APACHE III score, primary ICU admission diagnosis, and treatment location before ICU admission provided greater accuracy in prediction (ROC = 0.80) than the individual PaO2/FIO2 (ROC = 0.68). Patients were given an individual risk of hospital mortality based on their admission APACHE III score, treatment location before ICU admission, and ICU admitting diagnosis. Dividing the patient population into groups using a PaO2/FIO2 < or = 150 resulted in a wide range of individual risk for hospital mortality, from < 10 to > 90% in both groups. We conclude that ARDS is a complex clinical entity with a variety of pulmonary and nonpulmonary risk factors for both its development and its prognosis. Current and proposed categorical definitions based on the severity of hypoxemia result in a wide distribution of individual patient risks. Use of these findings in the design and conduct of future clinical trials would improve the evaluation of new therapies.

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Multiple organ system failure or dysfunction (MOSF/MODS) remains a major cause of morbidity and mortality in hospitalized adults. Among intensive care unit (ICU) patients the extent of physiologic derangement, the type of associated disease or injury, increasing age, and life-threatening comorbid conditions are the major determinants of risk for developing MOSF and for survival during the 1980s. Hospital mortality for patients with a single organ system failure (OSF) lasting more than 1 day approached 40%; and for those with two OSFs hospital mortality increased to 60%. These outcomes did not change over the decade. For patients with three or more OSFs persisting after 3 days of OSF, however, data suggest that between 1982 and 1990 the mortality has been reduced from 98% to 84% (p = 0.0003). Because of variations in the types and combinations of OSFs, associated disease, and extent of physiologic derangement, it is difficult to interpret variations in mortality among patients with one or more OSFs defined using categorical criteria. For this and other reasons, outcome prediction based on a comprehensive assessment of patient risk factors is a more sensitive, specific, useful approach to quantifying MODS than a simple count of the number and duration of OSFs. Because repeated assessment of risk factors during subsequent ICU days reflects complications and response to therapy, daily outcome predictions are even more precise than estimates at ICU admission. The ability to more accurately predict survival from MODS/MOSF can improve our ability to test new therapies, evaluate how outcome has changed over time, and assess the efficacy of supportive therapy for individuals.

The APACHE III prognostic system was a good discriminator of hospital mortality for ICU admissions at 10 Brazilian ICUs. There was substantial and significant variation, however, in SMRs among the Brazilian ICUs, which suggests that further evaluations of international differences in intensive care using a common risk assessment system should be performed and factors associated with variations in risk-adjusted mortality scrutinized.

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