Sequential changes in the metabolic response to orthotopic liver transplantation during the first year after surgery.

OBJECTIVE: To quantify the sequential changes in the metabolic response occurring in patients with end-stage liver disease after orthotopic liver transplantation (OLT). SUMMARY BACKGROUND DATA: Detailed 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. METHODS: Fourteen 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. RESULTS: Resting 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. CONCLUSIONS: Before 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.

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.

Overview of modern management of patients with critical injury and severe sepsis.

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.

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.

Transfusion transmitted Yersinia enterocolitica infection in New Zealand.

AIMS: To update and summarise cases of transfusion-transmitted Yersinia enterocolitica infection in New Zealand and to evaluate critically suggested methods to reduce this rare but frequently fatal complication of blood transfusion. METHODS: Case reports of four recent transfusion-transmitted Y. enterocolitica infections in New Zealand are given and previous reports reviewed. Literature review and evaluation of proposed methods to decrease the incidence of transfusing yersinia contaminated blood. RESULTS: There have been eight cases of transfusion-transmitted Y. enterocolitica infection in New Zealand in the past five years. Four of the five deaths have been directly caused by the transfusion. This gives a transfusion incidence rate of one:65,000 and a fatality rate of one:104,000 units transfused. This fatality rate is more than 80 times higher than that reported in the United States. CONCLUSIONS: Why the incidence of transfusion-transmitted yersinia is so high is not clear, since we do not store blood as long as many other countries, particularly the United States. In Auckland, however, the cases came at a time when the number of yersinia isolates from the community is reported to be rising. Many suggestions for the prevention of this problem have been put forward reflecting the fact that there is as yet no perfect solution. Those which are easy to implement and cheap to perform are largely already in place and investigation is continuing into the other alternatives.

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.

Injury scaling at autopsy: the comparison with premortem clinical data.

The difference between injury scaling performed in the same patients on the basis of clinical information only and postmortem examination only is largely unknown. We compared scores in all 279 trauma patients who died in the Department of Critical Care Medicine at Auckland Hospital from 1982 through 1987 (93% blunt trauma, 4% penetrating trauma, 3% burns; median time until death--2 days) using both the 1980 and 1985 revisions of the Abbreviated Injury Scale (AIS-80, AIS-85) and derived Injury Severity Scores (ISS-80, ISS-85) where such scoring was based on clinical information only (CLAIS, CLISS) or postmortem findings only (PMAIS, PMISS). For the group as a whole, there was little difference in the distribution of scores between CLAIS and PMAIS or between CLISS and PMISS. However, CLISS-80 was different from PMISS-80 in 68% of individual patients. Most major differences between CLAIS and PMAIS (two AIS grades or more) occurred in the Head region, where injury scoring based on physiological features (e.g. coma) occurred without an anatomic injury of similar AIS grade, or in the Thorax region where therapy had either abolished the evidence of injury (e.g. pneumothorax) or injuries were discovered at postmortem examination which had not been appreciated clinically. Injury scaling data derived only from postmortem examination is not equivalent to that derived clinically. For maximum accuracy, postmortem data must be derived from an examination specifically guided by the needs of injury scaling and in full cognizance of injuries recognised and treated clinically.

A comparison of AIS-85 with AIS-80 for injury scaling in blunt trauma.

As the effects on injury scaling of the differences between the 1980 and 1985 revisions of the AIS are unknown in blunt trauma, we compared them in all 1270 critically injured (median ISS, 26) blunt trauma patients (75% male, 74% road crash, overall mortality 17%) admitted to the Department of Critical Care Medicine at Auckland Hospital from 1983 through 1987. In 911 patients (72%) there were no differences between AIS-80 and AIS-85 in any body region or in derived ISS. Changes in AIS grades were most common in the abdomen (205 patients), thorax (100 patients), and head (61 patients) regions. Median ISS overall for the 1270 patients was unchanged at 26. One percent of patients had changes in ISS of 16-24 points. Direct comparison of groups of patients scored with these two revisions of the AIS is inappropriate, particularly in those with abdomen region injury.

Trauma in Auckland: an overview.

Data are presented on all 569 subjects who, as a result of trauma, either died or were admitted to hospital in Auckland over a four week period. Median age was 23 with an overall 3:2 male:female ratio. Median injury severity score (ISS) was five with 9% of subjects having an ISS of 16 or more (major trauma). Blunt trauma accounted for 84% of all injuries. Life threatening injuries were most commonly to the head, thorax and abdomen while the largest number of less severe injuries were to the extremities. Eight subjects died before admission to hospital and a further six in hospital. Definitive care was given to 98% of patients at Middlemore and Auckland hospitals (including the onsite Princess Mary paediatric facility) but 26% had presented first to other hospitals and 43% of all patients were transferred from one hospital to another. The 561 patients used 6380 hospital days (including 314 intensive care days) and the following services--operating room 63%, orthopaedic ward 45%, plastic surgical ward 17%, paediatric ward 15%, neurosurgical ward 10%, general surgical ward 5%, intensive care 5% and CT scanner 4%. Only one hospital death was judged potentially preventable. This study reveals areas where trauma care could be improved, demonstrates the large amount of hospital resources required to treat trauma and particularly highlights the urgent need for studies into strategies for trauma prevention in New Zealand.

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.

Measurement of total body chlorine by prompt gamma in vivo neutron activation analysis.

A method of measuring total body chlorine (TBCl) by prompt gamma in vivo neutron activation analysis is described which depends on the same NaI(Tl) spectra used for determinations of total body nitrogen. From these spectra counts ratios of chlorine to hydrogen are derived and TBCl is determined using a model of body composition which depends on measured body weight, total body water (by tritium dilution) and protein (6.25 X nitrogen) as well as estimated body minerals and glycogen. The precision of the method based on scanning an anthropomorphic phantom is at present only approximately 9% (SD), for a patient dose equivalent of less than 0.30 mSv. Spectra collected from 67 normal volunteers (32 male, 35 female) yielded mean values of TBCl of 72 +/- 19 (SD) g in males and 53.6 +/- 15 g in females, in broad agreement with values reported by workers using delayed gamma methods. Results are also presented for two human cadavers analysed both by neutron activation and by conventional chemical analysis; the ratios of TBCl (neutron activation) to TBCl (chemical) were 0.980 +/- 0.028 (SEM) and 0.91 +/- 0.09. Finally, it is suggested that an improvement in precision will be achieved by increasing the scanning time (thereby increasing the radiation dose equivalent) and by adding two more detectors.

Body composition of two human cadavers by neutron activation and chemical analysis.

In vivo neutron activation analysis (NAA) is currently used to measure body composition in metabolic and nutritional studies in many clinical situations, but has not previously been validated by comparison with chemical analysis of human cadavers. Total body nitrogen (TBN) and chlorine (TBCl) were measured in two human cadavers by NAA before homogenization and chemical analysis (CHEM) after (cadaver 1: TBN, 1.47 NAA, 1.51 CHEM; TBCl, 0.144 NAA, 0.147 CHEM; cadaver 2: TBN, 0.576 NAA, 0.572 CHEM; TBCl, 0.0227 NAA, 0.0250 CHEM). The homogenates were also analyzed by NAA, and no significant differences were found, indicating that the effects of elemental inhomogeneity on the measurement of TBN and TBCl are insignificant. Total body water, fat, protein, minerals, and carbohydrates were measured chemically for each cadaver and compared with estimates for these compartments obtained from a body composition model, which when used in vivo involves NAA and tritium dilution. The agreement found justifies the use of the model for the measurement of changes in total body protein, water, and fat in sequential studies in groups of patients.

Hydration of fat-free body in protein-depleted patients.

It is widely believed that increased hydration of the fat-free body accompanies most major disease processes as a result of contraction of the body cell mass and expansion of the extracellular fluid. Measurements of total body water (TBW) and total body nitrogen in 68 normal volunteers and 95 surgical ward patients presenting for intravenous nutrition have been used to derive ratios of TBW to fat-free mass (TBW:FFM) and protein indices (PI), where PI is defined as the ratio of measured total body protein to predicted TBP. Mean values of PI were 1.009 +/- 0.116 (SD) and 0.783 +/- 0.152 in the normal and patient groups, respectively, corresponding to mean TBW:FFM ratios of 0.719 +/- 0.016 and 0.741 +/- 0.029. However, 48 patients had normal TBW:FFM despite having lost 15% of body protein. A theoretical model of body composition changes in catabolic illness is presented, which is in accord with the patient data, demonstrating that TBW:FFM does not necessarily increase in catabolic illness and that the ratio masks underlying shifts in body fluid compartments.

Measurement of total body water in intensive care patients with fluid overload.

The measurement of total body water (TBW) in critically ill intensive care patients with greatly expanded TBW allows body composition studies to be undertaken in such patients with potentially important clinical consequences. Previous workers in this field have stressed the importance of the distortion of compartmental specific activity resulting from continued intravenous (IV) fluid administration during the period of equilibration and have made attempts to predict the equilibrium value of specific activity from the early arterial kinetics. In this paper a method for the measurement of TBW in critically ill intensive care patients is presented together with results of 16 studies on 11 such patients (mean TBW 54.61). It is shown that the effect of continued IV fluid administration in association with prolonged equilibration is small and that the prediction of TBW from analysis of the early (first hour) arterial kinetics is inappropriate. It is concluded that in such patients the volume of distribution of the isotope is constant after four hours from IV injection and that TBW can be measured with a mean precision of 0.7% (SD) from the fourth, fifth, and sixth hour measurements.

Measurement of body fat and hydration of the fat-free body in health and disease.

Body fat mass, fat-free body mass and body water are basic components of body composition which are used in nutritional and metabolic studies and in patient care. A method of measuring total body fat (TBF), fat-free mass (FFM) and its hydration (TBW/FFM) involving prompt gamma in vivo neutron activation analysis (IVNAA) and tritium dilution has been compared with the more traditional methods of densitometry and skinfold anthropometry in 36 normal volunteers, and with skinfold anthropometry in 56 patients presenting for nutritional support. While the mean values of TBF were in reasonable agreement for the three methods in normals it was founds that skinfold anthropometry underestimated TBF relative to the IVNAA/tritium method by, on average, 3.0 kg (19%) in patients. Furthermore, the ranges of values in normals of the ratio TBW/FFM for the anthropometric (0.62 to 0.80) and densitometric (0.65 to 0.80) methods were much wider than the range for the IVNAA/tritium method (0.69 to 0.76), in which TBW was measured by tritium dilution in all cases. In the patients, the ranges of this ratio were 0.52 to 0.90 for the anthropometric method and 0.67 to 0.82 for the IVNAA/tritium method; clearly anthropometry yields values of TBW/FFM which are outside accepted biological limits. On the basis of these findings, ranges of TBW/FFM are suggested for both normal adults (0.69 to 0.75) and patients requiring nutritional support (0.67 to 0.83). Finally it is concluded that the IVNAA/tritium method is a suitable method for measuring TBF and FFM and particularly so when body composition is abnormal.

Evaluation of an in vivo prompt gamma neutron activation facility for body composition studies in critically ill intensive care patients: results on 41 normals.

A programme of metabolic and nutritional research is being undertaken in critically ill patients requiring intensive care. Central to this research is the measurement of the three nutritionally important compartments of body composition, protein, fat, and water by a combination of tritium dilution and prompt gamma in vivo neutron activation analysis (IVNAA). In this paper a calibration technique is presented that enables absolute estimates of total body nitrogen (TBN) to be made using prompt gamma IVNAA in critically ill patients with gross abnormalities in body composition, especially in their state of hydration. This technique, which is independent of skinfold anthropometry and does not make a priori assumptions about the ratios of major body compartments, has been applied to 41 normal volunteers and the derived values for nitrogen compared with values obtained by applying three currently used calibration methods to the same experimental data; the other methods are used at centers which also measure nitrogen by prompt gamma IVNAA. Close agreement is obtained between the four calibration methods, with correlation coefficients relative to the Auckland technique of 0.999, 0.998, and 0.994. In addition, the measured values of TBN are compared to values obtained for the same group of volunteers using sets of empirical equations from two centers, one of which uses prompt gamma IVNAA (Brookhaven National Laboratory, Long Island, USA) and the other delayed gamma IVNAA (Leeds, Britain). The empirical equations relate TBN in normal people to age, height, weight and sex. The mean ratios of experimental to predicted TBN (with SEMs) are 1.013 +/- 0.017 and 1.002 +/- 0.014, respectively. Mean values of the ratio of TBN to fat-free mass (0.0340 +/- 0.0004) and of total body water to fat-free mass (0.716 +/- 0.002) agree closely with values reported elsewhere for normals by a variety of techniques including chemical analysis. Finally, TBN results based on the four different calibration methods are presented for five surgical patients, demonstrating the importance of the calibration method on estimates of TBN in patients with abnormal body composition. It is concluded that this technique will provide accurate estimates of the total body content of protein, water, and fat in intensive care patients.

Intentional paraquat poisoning: case report.

A case of intentional paraquat poisoning is presented. Early treatment was instituted. At four-month follow-up, the patient was well.