The strong ion gap does not have prognostic value in critically ill patients in a mixed medical/surgical adult ICU.

OBJECTIVE: To examine whether the strong ion gap (SIG) or standard base excess corrected for abnormalities of serum chloride and albumin (BE(UA)) can predict outcome and to compare the prognostic abilities of these variables with standard base excess (SBE), anion gap (AG), pH, and lactate, the more traditional markers of acid-base disturbance. DESIGN: Prospective, observational study. SETTING: University teaching hospital, general adult ICU. PATIENTS: One hundred consecutive patients on admission to the ICU. MEASUREMENTS AND RESULTS: The anion gap (AG) was calculated and corrected for abnormal serum albumin (AG(corrected)). Serum lactate was measured and SBE, BE(UA), SIG, and APACHE II scores calculated for each patient. 28-day survival was recorded. There was a significant difference between the mean APACHE II (P < 0.001), SBE (P < 0.001), lactate (P = 0.008), AG (P = 0.007), pH (P < 0.001), and BE(UA) (P = 0.009) of survivors and non-survivors. There was no significant difference between the mean SIG (P = 0.088), SIDeff (P = 0.025), and SID app (P = 0.254) between survivors and non-survivors. The pH and SBE demonstrated the best ability of the acid-base variables to predict outcome (AUROC curves 0.72 and 0.71, respectively). Neither of these were as good as the APACHE II score (AUROC 0.76) CONCLUSION: Traditional indices of SBE, BE(UA,) lactate, pH, AG, and APACHE II all discriminated well between survivors and non-survivors. In this group of patients the SIG, SIDeff, and SIGapp appear to offer no advantage in prediction of outcome and their use as prognostic markers can therefore not be advocated.

Acid-base physiology: the 'traditional' and the 'modern' approaches.

The interpretation and understanding of acid-base dysfunction has recently been revisited. The 'traditional' approach developed from the pioneering work of Henderson and Hasselbalch and is still the most widely used in clinical practice. There are a number of problems identified with this approach, however. The 'modern' approach derives from Stewart's work in physical chemistry. In this review we describe the origins of the traditional approach and discusses related concepts. We then describe Stewart's approach, including how it is derived and how it may be used to classify acid-base derangements. The applications of Stewart's approach to clinical scenarios in intensive care is then discussed briefly before we examine some published clinical studies based on his work.

The role of practice and automaticity in temporal and nontemporal dual-task performance.

Research on time and attention shows that a nontemporal task may interfere with a concurrent timing task by making time judgments shorter, more variable, and/or more inaccurate compared to timing-only conditions. Brown (1998, Psychological Research, 61, 71-81) counteracted the interference effect by giving subjects automaticity training on a nontemporal task to reduce the amount of processing resources the task required. Such practice attenuated interference in timing. Two new experiments were designed to replicate and extend the previous findings. Subjects generated a series of 5-s temporal productions under single-task (timing only) and dual-task (timing plus nontemporal task) conditions. The nontemporal tasks were pursuit rotor tracking (Experiment 1), and mirror-reversed reading (Experiment 2). We employed a pretest-practice-posttest paradigm, with the practice sessions devoted to performance of the nontemporal task. Pretest-posttest comparisons showed that practice reduced interference in timing in both experiments. Dual-task probe trials were given during the practice sessions to trace the time course of the improvement in timing. The results showed that interference in timing was reduced with even small amounts of practice. The findings support the idea that timing is very sensitive to changes in the allocation of attentional resources.

Prognostic factors in intensive care.

Predicting the outcome of critical illness remains an evolving art despite many recent advances. This review article describes the tools currently employed, appraising each in turn. The subject is viewed from the perspective that physiological reserve and inflammatory response are the essential elements in assessing prognosis in patients with multi-organ dysfunction/failure, the most commonly encountered syndrome in intensive care practice.

Base excess and lactate as prognostic indicators for patients admitted to intensive care.

OBJECTIVE: To examine whether values of arterial base excess or lactate taken on admission to a general intensive care unit indicate prognosis, and whether this can be used as a screening tool for future intensive care admissions. DESIGN: Observational study. SETTING: University teaching hospital general adult intensive care unit. PATIENTS: 148 consecutive patients admitted to the intensive care unit. INTERVENTIONS: Arterial blood samples were obtained on admission to the intensive care unit and 24 h following admission. MEASUREMENTS AND RESULTS: Arterial base excess and lactate concentrations were measured from the blood samples. Both base excess and arterial lactate samples on admission have good prognostic abilities (area under the curve on receiver operator characteristic analysis of 0.73, 0.78, respectively). The value of base excess on admission with the best predictive ability was a base excess more negative than -4 mmol/l, and the corresponding value for lactate was greater than 1.5 mmol/l. The combination of these two markers on admission to the intensive care unit led to a sensitivity of 80.3 % and a specificity of 58.7 % for mortality. The achievement of this combination was associated with an increased mortality (50.6 % vs. 15 %, p < 0.0001), older age (70 vs. 61.5 years, p < 0.05), a greater requirement for inotropic support (30.9 % vs. 4.5%, p < 0.0001) and higher organ failure scores both on admission and for the subsequent 24 h. CONCLUSIONS: Both base excess and lactate, or the combination of the two, can be used to predict outcome in patients admitted to the intensive care unit. These variables could be utilized to identify patients who have a high risk for mortality and thus who should be admitted to the intensive care unit.

Pathophysiology of septic encephalopathy: a review.

OBJECTIVES: Encephalopathy is a common complication of sepsis. This review describes the different pathologic mechanisms that may be involved in its etiology. DATA SOURCES: The studies described here were derived from the database PubMed (http:¿¿www.nlm.nih.gov) and from references identified in the bibliographies of pertinent articles and books. The citations are largely confined to English language articles between 1966 and 1998. Older publications were used if they were of historical significance. STUDY SELECTION: All investigations in which any aspect of septic encephalopathy was reported were included. This selection encompasses clinical, animal, and in vitro cell culture work. DATA EXTRACTION: The literature cited was published in peer-reviewed clinical or basic science journals or in books. DATA SYNTHESIS: Contradictions between the results of published studies are discussed. CONCLUSIONS: The most immediate and serious complication of septic encephalopathy is impaired consciousness, for which the patient may require ventilation. The etiology of septic encephalopathy involves reduced cerebral blood flow and oxygen extraction by the brain, cerebral edema, and disruption of the blood-brain barrier that may arise from the action of inflammatory mediators on the cerebrovascular endothelium, abnormal neurotransmitter composition of the reticular activating system, impaired astrocyte function, and neuronal degeneration. Currently, there is no treatment.

A prospective study of the use of a dobutamine stress test to identify outcome in patients with sepsis, severe sepsis, or septic shock.

OBJECTIVE: To more clearly define the relationship between an oxygen flux test, oxygen supply dependency, and outcome in patients with sepsis, severe sepsis, or septic shock. DESIGN: Prospective, interventional clinical trial. SETTING: A teaching hospital general intensive care unit in London, UK. PATIENTS: A total of 36 patients with sepsis, severe sepsis, or septic shock were studied during a 10-month period. INTERVENTIONS: After resuscitation, patients were given an intravenous infusion of dobutamine at 10 microg/kg/min for 1 hr. Cardiac and respiratory variables were measured before the infusion and then while the infusion was in progress. Any patient who was able to increase his or her oxygen consumption by >15% was designated a responder to the test. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, oxygen transport, and lactate measurements were made at baseline and after 1 hr of the dobutamine infusion. All patients were then followed up until hospital discharge. Responders to this test had a hospital mortality of 14%, whereas nonresponders had a mortality of 91% (p<.01). The responders were characterized by being younger (p<.05), having higher Acute Physiology and Chronic Health Evaluation III scores (p<.05), and having a greater requirement for inotropic support (p<.05). After the test, the responders had significantly higher oxygen delivery (p<.01) and oxygen consumption (p<.05) than the nonresponders, as well as a significantly greater temperature increase as a result of the infusion (p<.05). The nonresponders were unable to increase either oxygen delivery or oxygen consumption to the dobutamine. This test was highly predictive of outcome (p<.0001). The identification of an increase in both oxygen delivery and oxygen consumption (oxygen supply dependency) was not associated with a poor outcome. CONCLUSION: A dobutamine oxygen flux test provides evidence of the intrinsic function of cells. The inability of these cells to increase oxidative metabolism during sepsis, as indicated by the dobutamine test, is associated with a high mortality.

Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex.

Encephalopathy is a common complication of sepsis. However, little is known about the morphological changes that occur in the brain during sepsis. Faecal peritonitis was induced in pigs that were killed 8 h later and frontal cortex samples were taken immediately after death. The tissue was investigated using light and electron microscopy and compared with frontal cortex samples taken from sham-operated controls. Septic pigs had 49.5% more perimicrovessel oedema than sham pigs. However, the tight junctions between cerebral microvessel endothelial cells appeared morphologically intact in both septic and sham pigs. Sepsis also resulted in neuronal injury, disruption of astrocytic end-feet and swollen, rounded erythrocytes. These morphological changes may be sufficient to underlie the clinical features seen in septic encephalopathy.

Comparison of outcome from intensive care admission after adjustment for case mix by the APACHE III prognostic system.

STUDY OBJECTIVES: To evaluate the acute physiology, age, chronic health evaluation III (APACHE III) scoring system in the context of general adult ICUs in the United Kingdom. DESIGN: Prospective, noninterventional, cohort study. SETTING: Seventeen general adult ICUs in a discrete area of southwest England. PATIENTS: 12,793 patients admitted between April 1, 1993 and December 31, 1995. MEASUREMENTS: Sociodemographic and severity-of-illness data were collected for all patients admitted to the study units. Formal goodness-of-fit tests were applied and observed mortality was compared with that predicted by using the APACHE III system. RESULTS: For the group of ICUs as a whole, the risk-adjusted standardized mortality ratio (SMR) was 1.23 (95% confidence intervals, 1.12-1.25). For 11 out of 17 ICUs, the SMR was significantly greater than unity (p < 0.05). Calibration, as tested by Hosmer-Lemeshow statistics, was poor (H2 = 312.54; C2 = 332.85; df = 8; p < 0.01); however, model discrimination was good with a total correct classification rate of 82.9% and an area under the receiver operating characteristic curve of 0.89. CONCLUSIONS: The excess mortality observed after case-mix adjustment using the APACHE III system in this study may be the result of either poor intensive care performance as compared with the United States or a failure of the APACHE III equation to fit the UK data.

A cost analysis of a treatment policy of a deliberate perioperative increase in oxygen delivery in high risk surgical patients.

OBJECTIVE: To investigate the cost implications of a treatment policy of a deliberate perioperative increase of oxygen delivery in high risk surgical patients. DESIGN: A cost-effectiveness analysis comparing 'protocol' high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min/m2 with 'control' patients. INTERVENTIONS: In a randomised, controlled clinical trial we previously demonstrated a significant reduction in mortality (5.7% vs 22.2%, p = 0.015) and morbidity (0.68 +/- 0.16 complications vs 1.35 +/- 0.20, p = 0.008) in 'protocol' high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min per m2 compared with 'control' patients. This current study retrospectively analysed the medical care and National Health Service resource use of each patient in the trial. Departmental purchasing records and business managers were consulted to identify the unit cost of these resources, and thereby the cost of treating each patient was calculated. RESULTS: The median cost of treating a protocol patient was lower than for a control patient (6,525 pounds vs 7,784 pounds) and this reduction was due mainly to a decrease in the cost of treating postoperative complications (median 213 pounds vs 668 pounds). The cost of obtaining a survivor was 31% lower in the protocol group. CONCLUSION: Perioperative increase of oxygen delivery in high risk surgical patients not only improves survival, but also provides an actual and relative cost saving. This may have important implications for the management of these patients and the funding of intensive care.

Tracheal dilatation complicating prolonged tracheal intubation.

A patient with severe acute respiratory distress syndrome requiring prolonged tracheal intubation and mechanical ventilation is described. Tracheal dilation was noted to have occurred following an elective surgical tracheostomy. Eventually, the patient was successfully weaned from mechanical ventilation and the tracheostomy tube removed.

Changes in cardiac output during air ambulance repatriation.

OBJECTIVES: To measure, with the use of suprasternal Doppler ultrasound, the hemodynamic changes in patients and volunteers during air ambulance repatriation. DESIGN: Unblinded prospective observational study. SETTING: Chartered air ambulances for the international repatriation of patients. PATIENTS AND PARTICIPANTS: Six medical crew members and seven patients transported back to hospitals in the UK. INTERVENTIONS: The measurement of non-invasive blood pressure, ECG, heart rate, oxygen saturation and hemodynamic variables with suprasternal Doppler. MEASUREMENTS AND RESULTS: There was a drop in systolic and mean arterial blood pressure in the patient's group once in the air. Oxygen saturation dropped in both groups once at cruising altitude. Heart rate remained unchanged. Stroke distance and minute distance increased significantly in the patient's group and non-significantly in the volunteers. Peak velocity increased significantly in the patient's group. There was an overall reduction of systemic vascular resistance during take off and once at cruising altitude. CONCLUSIONS: Hemodynamic changes happen during air ambulance transportation in fit and healthy volunteers and patients alike. These may be due to a combination of hypobaric hypoxia and gravitational forces. It is necessary to establish if these changes have short- or long-term effects in the critically ill.

Plasma proinflammatory cytokine concentrations, Acute Physiology and Chronic Health Evaluation (APACHE) III scores and survival in patients in an intensive care unit.

OBJECTIVE: To more clearly define the relationships between plasma proinflammatory cytokine concentrations, physiologic disturbance, and survival in severely ill patients. DESIGN: Prospective, longitudinal, cohort analytic study. SETTING: Teaching hospital intensive care unit (ICU). PATIENTS: Two hundred fifty-one consecutive nonselected patients admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily Acute Physiology and Chronic Health Evaluation (APACHE) III scores were calculated from clinical and laboratory data. In concurrent blood samples, plasma concentrations were measured of four proinflammatory cytokines (tumor necrosis factor-[TNF] alpha, interleukin [IL]-1 beta, IL-6, and IL-8), all of which are believed to be of central importance in host proinflammatory and immune responses. Plasma TNF concentrations were increased in 42 patients, plasma IL-1 beta in 15 patients, IL-6 in 194 patients, and IL-8 in 52 patients at presentation. Although admission plasma IL-1 beta, IL-6, and IL-8 concentrations were higher in patients who died in the ICU compared with survivors (n = 33; p < .02, p < .01, p < .02, respectively), only admission plasma IL-8 concentrations were higher in patients with a fatal outcome if all in-hospital deaths were considered (n = 53; p = .05). APACHE III score was the best predictor of mortality (odds ratio 11.41; p = .003). Detection, but not the absolute level, of TNF bioactivity in plasma was a weak independent predictor of death (odds ratio 3.17; p = .02). There was no relationship between bacteremia or presence of the systemic inflammatory response syndrome and plasma cytokine concentrations. Nineteen patients were in the ICU for > or = 10 days, and of these 19 patients, 16 patients had prolonged increases of plasma cytokines. Two patients with persistently increased plasma TNF concentrations died. Otherwise, persistently increased plasma cytokine concentrations had a variable relation to daily APACHE scores and to mortality. CONCLUSIONS: Plasma cytokine concentrations fluctuate in serious illness and have a poor correlation with derangement of whole body physiology in seriously ill patients. Only the presence of bioactive TNF in plasma was an independent predictor of mortality. Daily measurement of plasma proinflammatory cytokine concentrations is unlikely to have clinical application in the ICU setting, except possibly in specific subgroups of patients.

Enhancement of perioperative tissue perfusion as a therapeutic strategy for major surgery.

Multiple organ dysfunction syndrome (MODS) accounts for most surgical deaths which occur some days postoperatively. Current hypotheses concerning the pathophysiology of MODS place tissue hypoxia and reperfusion as a central feature of the initiation and continuation of the syndrome. Surgical patients are at risk of developing overt and covert tissue hypoxia and hypoperfusion due to anesthetic, surgical, and other factors; and it is known that surgical patients with poor cardiovascular reserve have a worse outcome postoperatively. A number of clinical studies have attempted to intervene early in surgical patients to prophylactically improve tissue perfusion in the perioperative period by augmentation of cardiac output. These studies demonstrate a reduction in mortality and morbidity in these groups of patients. A similar approach has been tried in other groups of critically ill patients, at a later state in the evolution of their illness; these studies have not shown any improvement in outcome. In surgical patients, data show that those with more coexisting pathology and worse cardiac function may benefit most from a treatment approach aimed at improving tissue perfusion; furthermore, this may result in cost savings. The implications for the management of the higher risk surgical patient are obvious. It may no longer be acceptable to undertake surgery in these patients without facilities to monitor and improve cardiac output and tissue perfusion.