Variation in timing of decisions to withdraw life-sustaining treatment in adult ICU patients from three centres in different geographies: Do clinical factors explain the difference?

Background: Decisions to withdraw life-sustaining treatment (WLST) are common in intensive care units (ICUs). Clinical and non-clinical factors are important, although the extent to which each plays a part is uncertain. Objectives: To determine whether the timing of decisions to WLST varies between ICUs in a single centre in three countries and whether differences in timing are explained by differences in clinical decision-making. Methods: The study involved a convenience sample of three adult ICUs - one in each of the UK, USA and South Africa (SA). Data were prospectively collected on patients whose life-sustaining treatment was withdrawn over three months. The timing of decisions was collected, as were patients' premorbid functional status and illness severity 24 hours prior to decision to WLST. Multivariate analysis was used to identify factors associated with decisions to WLST. Clinicians participated in interviews involving hypothetical case studies devoid of non-clinical factors. Results: Deaths following WLST accounted for 23% of all deaths during the study period at the USA site v. 37% (UK site) and 70% (SA site) (p<0.0010 across the three sites). Length of stay (LOS) prior to WLST decision varied between sites. Controlling for performance status, age, and illness severity, study site predicted LOS prior to decision (p<0.0010). In the hypothetical cases, LOS prior to WLST was higher for USA clinicians (p<0.017). Conclusion: There is variation in the proportion of ICU patients in whom WLST occurs and the timing of these decisions between sites; differences in clinical decision-making may explain the variation observed, although clinical and non-clinical factors are inextricably linked. Contributions of the study: This study has identified variation in the timing of decisions to withdraw life-sustaining treatment in adult ICUs in three centres in three different healthcare systems. Although differences in clinical decision-making likely explain some of the variation, non-clinical factors (relating to the society in which the clinicians live and work) may also play a part.

Cadmium reduces extraocular muscle contractility in vitro and in vivo.

Cadmium, a blocker of calcium channels in various excitable cells, reduces the contractility of extraocular muscles. When applied to rat extraocular muscles in vitro, it reduces the sustained or tonic tension generated by the tonic multiply innervated fibers of the global layer of the muscles. When injected in vivo into rabbit extraocular muscles, it produces a temporary paralysis of the muscles and a deviation of the eye position. These effects are presumed to involve a blockade of the calcium channels of the muscle fibers and of the neuromuscular junctions. It is proposed that, on the basis of these effects, a non-surgical treatment of strabismus could be developed.

CPAP mask management of varicella-induced respiratory failure.

Pneumonia is a complication of primary varicella infection that occurs most commonly in adults and may lead to life-threatening respiratory failure. We report a case of varicella pneumonia with impending respiratory failure in which endotracheal intubation was averted by the use of CPAP mask ventilation with a favorable outcome.

Neuromuscular blocking agents in the emergency department.

Neuromuscular blocking agents (NMBAs) are utilized frequently in the emergency department (ED). We begin with a brief history of neuromuscular blockade, then review the indications and guidelines for its use in the emergency department setting. The relevant agents will be discussed focusing on dosage, side effects, and adverse reactions. Special attention will be paid to succinylcholine, the drug most commonly employed in the ED setting, followed by a summary of the nondepolarizing agents currently available, in particular the four shorter-acting agents that are most appropriate for administration in the ED.

Hypothermia. Saving patients from the big chill.

Although hypothermia is a serious and sometimes fatal condition, prompt recognition and institution of appropriate rewarming techniques may save even profoundly affected persons. The diagnosis of hypothermia should be considered when patients present with alterations of cerebral function without apparent explanation, especially in the presence of underlying predisposing illnesses and conditions. When hypothermia is suspected, an accurate core temperature must be obtained. Application of rewarming techniques appropriate to the degree of hypothermia may be lifesaving. Conservative use of pharmacotherapy is warranted.

Carbon monoxide poisoning. An occult epidemic.

Carbon monoxide poisoning is a significant health threat in the United States. Smoke inhalation from fires is the most common source. History of carbon monoxide exposure and elevated carboxyhemoglobin levels should alert physicians to the diagnosis of acute poisoning. When there is no history of exposure, carbon monoxide poisoning must be considered when two or more patients are similarly or simultaneously sick. The diagnosis must be excluded by a directed history and physical examination. If suspicion remains, carboxyhemoglobin levels should be determined and oxygen therapy should be started empirically while laboratory results are pending. Prompt administration of hyperbaric oxygen may reduce the risk of death. If carbon monoxide poisoning is confirmed, the source must be identified and recommendations for correction or avoidance should be made.

Perioperative renal protection.

Acute renal failure continues to complicate the postoperative courses of our vascular and cardiac surgical patients, dramatically increasing mortality and decreasing quality of life when it occcurs. In spite of better understanding of the disease, few gains have been made in its prevention. We review its pathophysiology and discuss the most recent developments that may eventually lead to perioperative renal protection.

Quantitative sacroiliac joint scintigraphy. A critical assessment.

With quantitative sacroiliac joint scintigraphy (QSS), sacroiliac joint-to-sacrum (SIS) ratios greater than or equal to 1.40 are abnormal for our method. High SIS ratios are associated with roentgenographically appreciated sacroiliitis and with early clinically evident sacroiliitis. Although highly sensitive, QSS abnormalities are not specific for inflammatory sacroiliac (SI) joint disease. High SIS ratios are also seen in rheumatoid arthritis, degenerative abnormalities of the lumbosacral spine, and metabolic bone disorder. Other disorders with roentgenographic SI joint abnormalities must be studied scintigraphically before QSS can be employed as a useful diagnostic test.

The association between preoperative patient characteristics and both clinical and economic outcomes after abdominal aortic surgery.

OBJECTIVE: To evaluate the association between patient characteristics and both clinical and economic outcomes in patients having abdominal aortic surgery in Maryland between 1994 and 1996. DESIGN: Retrospective study using an administrative data set. SETTING: All Maryland hospitals that performed abdominal aortic surgery from 1994 through 1996 (n = 46). PARTICIPANTS: All patients who had abdominal aortic surgery in Maryland from 1994 through 1996 (n = 2,987). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors obtained discharge abstracts from the Maryland Health Services Cost Review Commission for patients with a primary procedure code for abdominal aortic surgery. Primary outcome variables were in-hospital mortality, hospital length of stay, and intensive care unit (ICU) days. The authors evaluated the following groups of independent variables: demographic characteristics, severity of illness, comorbid disease, and preoperative admission days. In multivariate analysis, independent predictors of in-hospital mortality were age 61 to 70 years (odds ratio [OR], 3.1; confidence interval [CI], 1.4 to 6.9), age 71 to 84 years (OR, 7.2; CI, 3.7 to 14.1), age 85 years or older (OR, 9.3; CI, 3.9 to 21.9), ruptured aneurysm (OR, 5.3; CI, 3.5 to 8.2), urgent operation (OR, 2.3; CI, 1.1 to 5.2), emergent operation (OR, 3.0; CI, 1.9 to 4.7), mild liver disease (OR, 4.6; CI, 2.0 to 10.9), and chronic renal disease (OR, 6.9; CI, 3.9 to 12.1). Hospital admission 1 to 2 days preoperatively was not associated with a difference in in-hospital mortality but was associated with a 31% increase in hospital days (CI, 23% to 40%) and a 38% increase in ICU days (CI, 19% to 60%). CONCLUSION: In patients having aortic surgery, several patient characteristics such as mild liver disease and chronic renal failure, were associated with increased in-hospital mortality and length of stay. The practice of admitting patients to the hospital 1 to 2 days before surgery should be reevaluated because this was not associated with reduced in-hospital mortality but was associated with increased hospital and ICU stay.

Ligand-stimulated beta 2-adrenergic receptor internalization via the constitutive endocytic pathway into rab5-containing endosomes.

The small GTPase rab5 appears to be rate-limiting for the constitutive internalization of transferrin receptor and for fluid-phase endocytosis. However, it is unknown whether rab5 regulates receptors whose internalization is stimulated by the binding of ligand, and whether such receptors change the underlying rate of the endocytic pathways they utilize. As a model for ligand-stimulated endocytosis, we used transfected HEK293 cells expressing high levels of an epitope-tagged human beta 2-adrenergic receptor. Nearly all receptors were on the cell surface in the absence of agonist, but within ten minutes of agonist addition > 50% of receptors internalized and colocalized extensively with rab5. Hypertonic sucrose blocked beta 2-adrenergic receptor internalization, as well as that of transferrin receptor, suggesting a clathrin-mediated process. In contrast, an inhibitor of potocytosis had little effect upon beta 2-adrenergic receptor internalization, suggesting that this process did not require active caveolae. Consistent with this finding, caveolin was not detectable in the 12 beta 6 line, as assessed by western blotting with a polyclonal anti-caveolin antibody. Stimulated receptor internalization did not affect the rate or capacity of the constitutive endocytic pathway since there was no detectable increase in fluid-phase endocytosis after addition of beta-agonist, nor was there a significant change in the amount of surface transferrin receptor. Altogether, these data suggest that beta 2-adrenergic receptors internalize by a clathrin-mediated and rab5-regulated constitutive endocytic pathway. Further, agonist-stimulated receptor internalization has no detectable effect upon the function of this pathway.