Stephen Streat

Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients

It is current clinical practice to give intravenous nutrition (IVN) to critically ill postoperative septic intensive care patients to prevent loss of body protein, although it has not hitherto been possible to confirm this by direct measurement of body composition. Using a neutron activation analysis facility adapted to provide an intensive care environment and tritiated water dilution we directly measured total body water, protein and fat before and after 10 days of IVN (mean daily non-protein energy and amino acid intakes 2,750 kcal and 127 gm) in eight adult intensive care patients. All patients had recovered from the septic shock syndrome but were still ventilator dependent at the start of IVN. Six patients survived to leave hospital. As a group, the patients lost 12.5% of body protein (mean loss 1.5 +/- SE 0.3 kg; p = 0.001) despite a gain in fat (mean 2.2 +/- 0.8 kg; p = 0.026). There were, in addition, large losses of body water in most patients (mean, 6.8 +/- 2.6 kg; p = 0.036). We conclude that substantial losses of body protein occur in critically ill septic patients despite aggressive nutritional support and that further research is urgently required on the fate of infused substrates and the efficacy of alternative nutritional therapies.

Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma.

BACKGROUND Understanding the changes in energy expenditure and body composition is essential for the optimal management of the critically injured, yet these changes have not been quantified within the current context of trauma care. METHODS Ten critically injured patients (median Injury Severity Score = 35) had measurements of energy expenditure and body composition as soon as they were hemodynamically stable and then every 5 days for 21 days. RESULTS Resting energy expenditure rose to 55% above predicted and remained elevated throughout the study period. Total energy expenditure was 1.32 X resting energy expenditure. Body fat was oxidized when energy intake was insufficient (r=-0.830, p<0.02). Body water changes closely paralleled body weight changes and were largely accounted for by changes in extracellular water. Over the 21-day study period, there was a loss of 1.62 kg (16%) of total body protein (p<0.0002), of which 1.09 kg (67%) came from skeletal muscle. Intracellular potassium was low (133 +/- 3 mmol/L, p<0.02) but did not deteriorate further after hemodynamic stability had been reached. CONCLUSIONS These results show that the period of hypermetabolism lasts longer and the protein loss is greater in critically injured patients than previously thought. Most, but not all, the protein is lost from muscle. Fat loss can be prevented and cell composition preserved once hemodynamic stability is achieved.

Surgeons, intensivists, and the covenant of care: administrative models and values affecting care at the end of life--Updated.

ContextEnd-of-life care remains a challenging and complex activity in critical care units. There is little information concerning the influence of administrative models of care delivery on end-of-life care. ObjectiveTo compare and contrast end-of-life care delivery in intensive care units using “semiclosed,” “open,” and “closed” administrative models. DesignEthnographic study of three critical care units. SettingUniversity hospitals in the United States and New Zealand. SubjectsApproximately 600 physicians, nurses, allied health personnel, patients, family members, and friends. Measurements and Main ResultsEthnographic observations were made at three sites for 75, 3, and 10 wks, respectively. Eighty end-of-life care episodes were observed. The interactions among care personnel and families varied according to the administrative model, depending on whether surgeons or intensivists had primary patient responsibility. This led to differential timing on the shift from “cure” to “comfort,” and differential decision-making power for families. ConclusionsEnd-of-life care varies according to the administrative model. When surgeons have primary responsibility for the patient, the most important goal is defeating death. When intensivists have sole patient responsibility, scarce resources are considered and quality of life is a significant variable. Discussions about improving the way end-of-life decisions are carried out in intensive care units rarely consider the administrative models and personal, professional, and national values affecting such decisions. To improve care at the end of life, we must critically examine these features.

Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis-a randomized, clinical trial

OBJECTIVES Tumor necrosis factor (TNF)-alpha appears central to the pathogenesis of severe sepsis, but aspects of the cytokine cascade and the link to physiologic responses are poorly defined. We hypothesized that a monoclonal antibody to TNF-alpha given early in the course of severe sepsis would modify the pattern of systemic cytokine release and, as a consequence, resuscitation fluid requirements, net proteolysis, and hypermetabolism would be reduced. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Critical Care Unit and University Department of Surgery in a single tertiary care center. PATIENTS Fifty-six patients (from 92 eligible patients) with severe sepsis. Twenty-eight patients were randomized to treatment, and were comparable with the placebo group for age, gender, race, Acute Physiology and Chronic Health Evaluation II score, and site and type of infection. INTERVENTIONS A 300-mg single dose of cA2 (a chimeric neutralizing antibody to TNF-alpha) was given intravenously within 12 hrs of the onset of severe sepsis. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS Plasma concentrations of TNF-alpha, interleukin (IL)-1beta IL-6, IL-8, IL-10, soluble 75-kilodalton TNF-alpha receptor (sTNFR-75), and IL-1beta receptor antagonist (IL-1ra) were measured by sandwich enzyme-linked immunosorbent assay before cA2 infusion, 8 hrs later, and then daily for a minimum of 4 days. Sequential changes in total body protein, body water spaces, and resting energy expenditure over 21 days were measured, as soon as patients achieved hemodynamic stability, by in vivo neutron activation analysis, tritium and bromide dilution, and indirect calorimetry, respectively. Twenty-one patients died, ten having received cA2. Suppression of measurable TNF-alpha was observed at 8 hrs with subsequent rebound by 24 hrs after cA2 treatment. The concentrations of other cytokines were high, were not reduced by intervention, and decreased logarithmically over 5 days. Both groups reached hemodynamic stability at similar times (57.5 +/- 11.8 hrs in controls vs. 58.6 +/- 9.2 hrs in the cA2 group) and following similar volumes of infused fluids (29.1 +/- 3.4 L vs. 28.9 +/- 4.4 L). No differences in net proteolysis, resolution of body water expansion, or alteration in resting energy expenditure were demonstrated. CONCLUSION A single dose of cA2 did not alter the overall pattern of cytokine activation or the profound derangements in physiologic function that accompany severe sepsis.

Bereavement follow-up after critical illness.

Objective: To describe the establishment and initial activity of a Bereavement Follow‐up Service for next‐of‐kin of patients who died in an intensive care unit (ICU) and to quantify aspects of their experience including quality of intensive care service and the early impact on next‐of‐kin of their bereavement. Design: Cross‐sectional prospective study, which was conducted by a structured telephone interview. Setting: A 14‐bed adult general ICU in a tertiary university hospital. Subjects: A total of 99 next‐of‐kin of patients who died in ICU. Interventions: Referral to other agencies if requested. Measurements and Main Results: Attempts were made to contact the next‐of‐kin of all 151 patients who died in 1995, and 104 were contacted. Five declined to be interviewed. The results refer to 99 who consented to telephone interview a median of 33 days after the death. A total of 84 considered themselves well informed during the intensive care period, 76 understood the fatal sequence of events but 19 of them would have liked more information. A total of 77 had positive comments about the quality of care, most commonly about compassionate behavior (58), but 30 had negative comments, most commonly about poor communication (13). Only 7 were living alone, 85 had resumed normal activities, 40 of 47 workers had returned to work, 58 had sleep disturbance at some stage (still present in 44), but only 12 were taking sedatives or antidepressants. A total of 32 had financial difficulties and 21 were referred to other agencies, most commonly grief counselors. Conclusions: We were disappointed to contact only two thirds of next‐of‐kin, but results from these subjects demonstrated a high level of satisfaction with the care given. Nevertheless, some were dissatisfied with the quality of service they experienced. Most had resumed their normal activities, including work, and few were living alone. However, sleep disturbance and financial difficulty were common, and some requested help from other support agencies.

Sequential Changes in the Metabolic Response to Orthotopic Liver Transplantation During the First Year After Surgery

ObjectiveTo quantify the sequential changes in the metabolic response occurring in patients with end-stage liver disease after orthotopic liver transplantation (OLT). Summary Background DataDetailed quantification of the changes in energy expenditure, body composition, and physiologic function that occur in patients after OLT has not been performed. Understanding these changes is essential for the optimal management of these patients. MethodsFourteen patients who underwent OLT for end-stage liver disease had measurements of resting energy expenditure, body composition, and physiologic function immediately before surgery and 5, 10, 15, 30, 90, 180, and 360 days later. ResultsResting energy expenditure was significantly elevated after surgery (24% above predicted), peaking around day 10 after OLT, when it averaged 42% above predicted. A significant degree of hypermetabolism was still present at 6 months, but at 12 months measured resting energy expenditure was close to predicted values. Before surgery, measured total body protein was 82% of estimated preillness total body protein. During the first 10 days after OLT, a further 1.0 kg (10%) of total body protein was lost, mostly from skeletal muscle. Only 54% of this loss was restored by 12 months. Significant overhydration of the fat-free body was seen before OLT, and it was still present 12 months later. Although significant losses of body fat and bone mineral occurred during the early postoperative period, only body fat stores were restored at 12 months. Both subjective fatigue score and voluntary hand grip strength improved rapidly after OLT to exceed preoperative levels at 3 months. At 12 months grip strength was close to values predicted for these patients when well. Respiratory muscle strength improved less markedly and was significantly lower than predicted normal levels at 12 months. ConclusionsBefore surgery, these patients were significantly protein-depleted, overhydrated, and hypermetabolic. After surgery, the period of hypermetabolism was prolonged, restoration of body protein stores was gradual and incomplete, and respiratory muscle strength failed to reach expected normal values. Our measurements indicate that OLT does not normalize body composition and function and imply that a continuing metabolic stress persists for at least 12 months after surgery.

Overview of Modern Management of Patients with Critical Injury and Severe Sepsis

Abstract. Over the last 10 years there have been substantial changes in the issues confronting intensivists and surgeons caring for critically ill patients. A substantial increase in the number of elderly patients with surgical illness and complex co-morbidity has accompanied the increase in the proportion of elderly in populations in the developed world. This phenomenon has been seen particularly with sepsis. Incidence rates for blunt trauma have declined overall, but the problems of the elderly trauma patient have become more evident. Major elective surgery remains a common indication for short-term intensive care in many countries, but the need for cost-containment has led to increased use of high-dependency care for many such patients. Expectations of both society and clinicians have increased, and this has been reflected in the increased demand for complex procedures (e.g., liver transplantation, cerebral artery aneurysm clipping, aortic aneurysm repair) in patients previously considered at too high risk. Along with these expectations have come pressures on clinicians to reduce costs at the same time as improving clinical outcomes. Despite many advances in the care of critically ill patients with injury or sepsis, mortality, morbidity, and cost remain high; and nutritional support is frequently required. The duration and extent of the metabolic changes seen in response to critical surgical illness and intensive care treatments have become better characterized. Although some of the changes in body water and fat are modifiable, loss of large amounts of (functional) protein has been resistant to various strategies so far studied.

Pro/con ethics debate: When is dead really dead?

Contemporary intensive care unit (ICU) medicine has complicated the issue of what constitutes death in a life support environment. Not only is the distinction between sapient life and prolongation of vital signs blurred but the concept of death itself has been made more complex. The demand for organs to facilitate transplantation promotes a strong incentive to define clinical death in a manner that most effectively supplies that demand. We consider the problem of defining death in the ICU as a function of viable organ availability for transplantation

Health Economics and Health Technology Assessment: Perspectives from Australia and New Zealand

Formal health economics and health technology assessment (HTA)processes, including cost-effectiveness and cost-utility analysis, are variably used to inform decisions about public and private health service funding and service provision. In general, pharmaceuticals have been subject to more sophisticated health economic analyses and HTAs and for a longer time than either devices or procedures. HTA has been performed by a number of different entities. While HTA shares many common features across the world, its uses, approaches, applications,and impact differ throughout the world. This article will discuss some of the general attributes of HTA and will focus on its specific applications in Australia and New Zealand.

Ethics roundtable debate: should a sedated dying patient be wakened to say goodbye to family?

Intensivists have the potential to maintain vital signs almost indefinitely, but not necessarily the potential to make moribund patients whole. Current ethical and legal mandates push patient autonomy to the forefront of care plans. When patients are incapable of expressing their preferences, surrogates are given proxy. It is unclear how these preferences extend to the very brink of inevitable death. Some say that patients should have the opportunity and authority to direct their death spiral. Others say it would be impossible for them to do so because an inevitable death spiral cannot be effectively palliated. Humane principles dictate they be spared the unrelenting discomfort surrounding death. The present case examines such a patient and the issues surrounding a unique end-of-life decision.