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Summary This study investigates the regulation of the insulin-like growth factors (IGFs) and their regulatory proteins in 14 critically ill patients during the 30-day period following admission to an intensive care unit (ICU). Levels of IGF-I, IGF-II, IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS) were low on admission, and in the 8 patients whose serum IGF-I levels failed to increase over 30 days, levels of the other proteins also remained low, while IGFBP-3 proteolytic activity increased. Of these proteins, ALS correlated best with serum levels of nutritional indicators, particularly prealbumin. IGFBP-2 and IGFBP-6 levels tended to be high in critically ill patients, but showed little change over the 30-day period. In contrast, IGFBP-1 levels were high on admission, correlated with early changes in nitrogen balance, and fell rapidly during the first week. By demonstrating that the IGF-I response in ICU patients is related to changes in the IGF regulatory proteins, this study may be of value in planning therapeutic intervention using growth hormone or IGF-I.

OBJECTIVE We aimed to concurrently characterize serial changes in circulating immunoreactive inhibin (irINH) and testosterone (T) as reflections of Sertoli and Leydig cell responses to acute critical illness in man. DESIGN Blood samples were drawn within 24 hours of admission to an Intensive Care Unit and at weekly intervals thereafter for up to 4 weeks while the patient remained in Intensive Care Unit or after discharge to a general ward. PATIENTS We studied 13 male subjects with critical illness requiring intensive therapy. MEASUREMENTS Plasma levels of irINH, T, LH, FSH and sex hormone binding globulin (SHBG) were analysed in relation to (i) the severity of illness as indicated by a sepsis score, acute physiology and chronic health evaluation score, and reverse triiodothyronine (rT3) levels and (ii) the outcome of illness as determined by discharge from Intensive Care Unit and the two-month mortality. RESULTS Overall irINH levels remained normal and correlated negatively with rT3 (r = -0.63, P = 0.001) but not with sepsis, acute physiology and chronic health evaluation score, or gonadotrophin levels. Neither admission nor serial irINH levels significantly distinguished between the different clinical outcomes. In contrast, T levels were depressed and inversely correlated with both sepsis and acute physiology and chronic health evaluation scores (P less than 0.02), and positively with gonadotrophins (P less than 0.01), but not rT3 levels. Men eventually discharged from the Intensive Care Unit showed a rise, while those remaining showed a fall, in T levels (P = 0.02, time-course interaction). Similarly, T levels were lower in patients who died than in survivors, despite the comparable T levels on admission (P = 0.02, time-course interaction). Despite the fall in T levels, gonadotrophin levels remained inappropriately in the eugonadal range but higher in men who were discharged from Intensive Care Unit (P = 0.02, time-course interaction). FSH but not LH levels were correlated with sepsis score (P = 0.02) but not acute physiology and chronic health evaluation score or rT3. CONCLUSIONS Sertoli cell function as judged by circulating irINH levels is much less affected by acute critical illness than is Leydig cell function as judged by circulating T levels. The suppressive effect of acute critical illness on Leydig cell function is consistent with a hypothalamic-pituitary lesion.

The liver is in some ways the forgotten organ in intensive care practice. Very many more laboratory and clinical studies have investigated the role, function, and support of the lung, heart, brain, and kidney in critical illness than have studied the liver. Nevertheless, in the time of the Greek scholars, there was already acknowledgement of the role of the liver in non-hepatic diseases such as systemic sepsis, and an understanding that such involvement confers a poorer prognosis – hence the inclusion of the wisdom of Hippocrates in this compilation of classic papers. In the review article by Matuschak and Rinaldo, the reasons why liver dysfunction is associated with a poorer outcome in critical illness are explored, and the concept of the liver being a ‘driving force’ in multiple organ dysfunction is developed. In addition, jaundice without significant liver dysfunction is associated with left ventricular dysfunction, at least in the dog model developed by Professor Otto Better and his colleagues in Israel. This observation is relevant to the progressive resistance to inotropic and vasopressor agents in jaundiced critically ill patients.

Sepsis is associated with profound catabolism and hypermetabolism that complicate provision of nutritional support. These metabolic changes are caused by inflammatory mediators involved in the septic process and cannot be reversed by nutritional means. High protein isocaloric nutritional regimens are recommended if possible, in association with aggressive measures to control the sepsis. However, nutritional therapy and its complications may also affect the incidence and course of sepsis. Hyperglycemia and conventional intravenous fat emulsions have been shown to increase susceptibility to infection. Enteral nutrition is associated with fewer infectious complications than parenteral nutrition, at least in severely injured patients. Recently nutritional formulations have been introduced that contain novel substrates that enhance various aspects of immunity. Several studies have suggested that this immunonutrition reduces infection risk in the critically ill, and preliminary findings suggest it may even have an effect on survival in sepsis.

A V ˙ / Q ˙ lung scan was obtained in a patient with LLL collapse who was receiving IPPV and PEEP. This revealed absent ventilation and hyperperfusion to the collapsed lobe. After a reduction in PEEP from 12 to 5 cm H 2 O, a repeat V ˙ / Q ˙ scan showed a more even distribution of pulmonary perfusion. Arterial hypoxemia improved.

Abnormal liver function commonly accompanies critical illness. Ischaemic hepatitis occurs with shock and is characterised by elevated plasma aminotransferase concentrations. ‘ICU jaundice’ occurs later in critical illness, especially after trauma and sepsis. The major biochemical abnormality is conjugated hyperbilirubinaemia. The clinical setting suggests that hepatic ischaemia and hepatotoxic actions of inflammatory mediators are the major aetiological factors. Massive blood transfusion, effects of nutritional support and drug toxicity may contribute. Both the presence and degree of jaundice are associated with increased mortality in several nonhepatic diseases. It is proposed that Kupffer cell phagocytic depression associated with liver dysfunction permits systemic spread of endotoxin and inflammatory mediators and thus predisposes to multiple organ failure. Immunosuppression, metabolic abnormalities, impaired drug oxidation and myocardial depression may contribute to the poor prognosis. There is no specific treatment, but prompt resuscitation, definitive treatment of sepsis and meticulous supportive care will likely reduce the incidence and severity.

Biochemical evidence of selenium (Se) deficiency is frequent in patients with chronic malnutrition. However, the incidence of Se deficiency in acutely ill patients is unknown. In 175 consecutive ICU patients, plasma Se measured during the first week of ICU admission was 0.66 +/- 0.21 mumol/L (mean +/- SD) and was less than that measured in 57 healthy blood donors (1.05 +/- 0.21 mumol/L, p less than .001). Sixty-eight percent of plasma Se concentrations fell below the lower limit of the reference range. Plasma Se decreased with the number of weeks in the ICU (r = .33, p less than .01) with values decreasing to 0.49 +/- 0.20 mumol/L during the fourth week. Urinary Se excretion measured in a subgroup of 20 patients was related to plasma Se concentration (r = .38, p less than .05), and inversely related to N balance (r = .50, p less than .01). We conclude that decreased plasma Se concentrations are common in ICU patients and that catabolic states are associated with increased Se losses. These losses are unlikely to account for the marked reductions in plasma Se concentrations, and the findings suggest there may be significant changes in the distribution of body Se during critical illness.

Digoxin-like immunoreactive substances are an endogenous group of compounds that cross-react in conventional immunoassays for digoxin. Plasma digoxin-like immunoreactive substance concentrations were estimated using the Abbott TDxll fluorescence polarisation immunoassay kit for digoxin. Digoxin-like immunoreactive substances were measured in one hundred consecutive Intensive Care Unit (ICU) patients who were not treated with digoxin. One hundred healthy blood donors were used as controls. Thirty of the ICU patients had plasma digoxin-like immunoreactive substance concentrations greater than or equal to the greatest value found in the control group (0.22 nmol/l). In the ICU group the median value was 0.17 nmol/l and the range zero to 1.69 nmol/l. In the control group the median was less than the limit of detection of the assay, and the range zero to 0.22 nmol/l. Sixteen ICU patients had coexisting renal and hepatic dysfunction and this group had a median digoxin-like immunoreactive substance concentration of 0.21 nmol/l (range zero to 1.69 nmol/l), while 38 patients with hepatic dysfunction and normal renal function had a median concentration of 0.17 nmol/l (range zero to 0.77 nmol/l). In contrast four patients with renal dysfunction only had a median concentration of 0.05 nmol/l (range zero to 0.34 nmol/l). The remaining forty-two patients had neither hepatic nor renal dysfunction and this group had a median concentration of 0.15 nmol/l (range zero to 0.36 nmol/l). This study has identified the critically ill as a group of patients who exhibit measurable plasma digoxin-like immunoreactive substances using the most commonly used kit for analysis of digoxin.

Objectives To determine the factors predicting mortality from bleeding esophageal varices and to examine the possibility of an association between the development of adult respiratory distress syndrome (ARDS) and the use of ethanolamine oleate as an esophageal variceal sclerosant. Design Retrospective review. Setting ICU in a teaching hospital. Patients A total of 101 patients with endoscopically confirmed bleeding esophageal varices were admitted on 124 occasions from 1985 to 1990. Mean age was 50 +/- 13.5 (SD) yrs. There were 62 males and 39 females. Using the Child-Pugh classification, 21.8% patients were class A, 38.6% class B, and 39.6% class C. Mean ICU and hospital lengths of stay were 5.4 +/- 5.1 and 19.6 +/- 16.1 days, respectively. Mean Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission was 16.5 +/- 7.6. Interventions Endoscopic variceal sclerotherapy was performed in 99 (79.8%) of 124 ICU admissions in the 101 patients. Esophageal balloon tamponade was performed in 64 (51.6%) and a vasopressin infusion was administered in 47 (37.9%) of the 124 ICU admissions. A variety of factors was studied to find predictors of mortality and the development of ARDS. Results Forty-eight (48.5%) of the 101 patients died during the hospital stay. Independent predictors of mortality (by stepdown logistic regression) were total volume of ethanolamine oleate injected during sclerotherapy, multiple blood transfusions, Glasgow Coma Scale score, International normalized ratio for prothrombin test, and the presence of circulatory shock on ICU admission. Age, sex, Child-Pugh score, APACHE II score, serum bilirubin, albumin, and creatinine concentrations, use of esophageal balloon tamponade or vasopressin infusion, sepsis, pneumonia, congestive cardiac failure, aspiration, and ARDS were not statistically independent predictors of outcome. There was no difference in the mortality rates for the various causes of liver disease. Pulmonary complications occurred in 44 (43.6%) patients; sepsis occurred in 31 (25%) patients. ARDS developed in 14 patients (11.3% admissions, 13.9% patients). Statistically independent predictors of ARDS were sepsis, low plasma albumin concentration, use of esophageal balloon tamponade, and more than one sclerotherapy session. The volume and type of sclerosant used were not statistically independent predictors. Conclusions Outcome is poor for patients with bleeding esophageal varices requiring ICU admission and is related to the severity of liver failure, the degree of blood loss, and failure of therapy to stop the bleeding. The findings do not support an association between the use of the sclerosant ethanolamine and the development of ARDS.

Twenty ICU patients, with varying diagnoses and degrees of catabolism, were studied prospectively to determine whether somatomedin-C/insulin-like growth factor I (SMC/IGFI) is related to the conventional nutritional indices, plasma prealbumin, transferrin and albumin, and nitrogen balance (NB) in critical illness. Mean SMC/IGFI concentration in these critically ill patients was below the lower limit of the reference range. SMC/IGFI concentrations correlated with NB for the 24 h before measurement (r = .38, p less than .01) and with cumulative NB for the previous 2 (r = .50, p less than .01), 3 (r = .34, p less than .05), and 5 days (r = .46, p less than .05). Prealbumin correlated with cumulative 5-day NB (r = .39, p less than .05). Plasma albumin and transferrin concentrations did not correlate with NB for any of these time periods. SMC/IGFI concentrations correlated with cumulative protein (r = .59, p less than .01), carbohydrate (r = .63, p less than .01), and energy intake (r = .64, p less than .01). SMC/IGFI was the only index which consistently correlated with NB. We conclude it is a useful index of nutritional status in critically ill patients.