Gastrointestinal permeability following cardiopulmonary bypass: a randomised study comparing the effects of dopamine and dopexamine.

OBJECTIVE: To compare the effects of dopexamine and dopamine on the mucosal permeability of the gastrointestinal tract (GIT). DESIGN: Prospective, randomised clinical trial. SETTING: Intensive care unit of a postgraduate teaching hospital, London, England. PATIENTS: Thirty patients undergoing elective surgery involving cardiopulmonary bypass, performed by a single surgeon. INTERVENTIONS: Patients were randomly assigned to receive either dopexamine 2.0 micrograms/kg per min or dopamine 2.5 micrograms/kg per min for the duration of the study period. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters and gastric intramucosal pH (pHi) were measured at intervals throughout the study. GIT permeability was measured once, post-operatively, using the ratio of absorbed lactulose to L-rhamnose. The groups were similar with respect to demographics, pre- and post-operative risk factors. The lactulose/rhamnose ratio was (mean +/- SEM) 0.44 +/- 0.10 in the dopexamine group vs 0.65 +/- 0.08 in that receiving dopamine (p < 0.05). The dopexamine group had a significantly higher oxygen delivery preoperatively (479.5 +/- 32.0 ml/min per m2 vs 344.4 +/- 23.9 ml/min per m2 for dopamine, p < 0.01), but no other significant differences emerged between the groups. CONCLUSIONS: Compared to dopamine, dopexamine reduces GIT permeability following surgery involving cardiopulmonary bypass. The mechanism of this effect remains unclear.

Pulmonary vascular permeability after cardiopulmonary bypass and its relationship to oxidative stress.

OBJECTIVE: To assess the relationship between oxidative stress resulting from cardiopulmonary bypass and the onset of increased pulmonary vascular permeability. DESIGN: Prospective, controlled study. SETTING: Adult intensive care unit of a postgraduate teaching hospital. PATIENTS: Ten patients undergoing surgery requiring cardiopulmonary bypass, and seven normal subjects. INTERVENTIONS: Cardiopulmonary bypass in ten patients undergoing surgery. MEASUREMENTS AND MAIN RESULTS: Protein accumulation index was measured in patients after surgery and in normal subjects as a marker of increased pulmonary vascular permeability. Plasma markers of lipid peroxidation (lipid peroxides and thiobarbituric acid-reactivity), plasma chelatable iron, total non-heme iron, transferrin, and primary plasma proteinaceous antioxidant activities were measured before and after cardiopulmonary bypass, and compared with those values found in normal subjects. Protein accumulation index was significantly higher (1.79 +/- 0.54 [SEM]) in the postcardiopulmonary bypass patients compared with healthy subjects (0.33 +/- 0.07, p < .05). Concentrations of lipid peroxides precardiopulmonary bypass were similar to those concentrations in control patients (0.020 +/- 0.003 vs. 0.031 +/- 0.002 nmol/mg protein), but were significantly increased postcardiopulmonary bypass (0.114 +/- 0.010 nmol/mg protein, p < .01). Thiobarbituric acid-reactive substances were higher precardiopulmonary bypass than those in controls (0.052 +/- 0.01 vs. 0.019 +/- 0.01), and increased postcardiopulmonary bypass (0.072 +/- 0.012), although they did not reach significance. Bleomycin-chelatable iron, indicative of transient plasma iron-overload, was only found in one patient (6.5 mumol/L) postcardiopulmonary bypass. Total plasma non-heme iron concentrations before cardiopulmonary bypass were similar to those concentrations in normal control patients (0.19 +/- 0.03 vs. 0.22 +/- 0.015 nmol/mg of protein), and significantly increased postcardiopulmonary bypass (0.48 +/- 0.08, p < .01). Transferrin concentrations were lower in cardiopulmonary bypass patients (2.43 +/- 0.17 vs. 2.89 +/- 0.03 g/L) than in controls and significantly decreased postcardiopulmonary bypass (1.55 +/- 0.09 g/L, p < .01). High plasma iron concentrations with a lower level of transferrin, postcardiopulmonary bypass, gave significantly increased mean percentage iron-saturation of transferrin, increasing from 27.1% to 61.7% (p < .01). Proteinaceous primary antioxidant activities, measuring iron-binding and iron-oxidizing protection of peroxidizing lipid membranes, were both significantly decreased postcardiopulmonary bypass (83.7 +/- 3.71% pre and 26.6 +/- 8.42% post, p < .01, and 51.2 +/- 2.96% pre and 29.0 +/- 2.94% post, p < .01, respectively). In 90% of the cardiopulmonary bypass patients, there was a significant correlation between the percent increase in iron saturation of transferrin and the protein accumulation index. CONCLUSIONS: Pulmonary vascular permeability was significantly increased in patients postcardiopulmonary bypass compared with normal subjects. This patient population also had significantly increased plasma markers of lipid peroxidation compared with normal subjects. Cardiopulmonary bypass induced further increases in lipid peroxidation products but a substantial decrease in proteinaceous primary antioxidants. In the majority of patients, there was a significant correlation between the iron saturation of transferrin and the protein accumulation index.

Severe pulmonary dysfunction following acute respiratory distress syndrome.

Recovery of lung function following the acute respiratory distress syndrome (ARDS) is thought to be related to the severity of the initial insult. We report a case demonstrating virtually complete functional recovery following severe ARDS. The significance of this and the need for comprehensive follow-up of such patients is discussed.

Effects of enteral and parenteral nutrition on gut mucosal permeability in the critically ill.

The use of total parenteral nutrition (TPN), in the critically ill, may be associated with the translocation of bacteria and their products from the lumen of the gastrointestinal tract (GIT) to the systemic circulation. We report a study comparing the effects of TPN and enteral nutrition (EN) on GIT function. Twenty-four critically ill patients were randomly allocated to receive TPN or EN. GIT absorption was measured by urinary recovery of D-xylose and 3-O-methyl-D-glucose (3O MG) after enteral administration. The ratio between urinary recovery of lactulose and L-rhamnose (L/R) was used to measure GIT mucosal permeability. Results are expressed as the percentage of enterally administered saccharide recovered. Measurements were performed at entry to the study and on every subsequent third day. Baseline recovery of D-xylose (5.95 +/- 1.61%, EN; 6.56 +/- 3.38%, TPN) and 3O MG (12.35 +/- 4.06%, EN; 7.96 +/- 4.19%, TPN) was significantly lower than for the controls (35.03 +/- 1.40% for D-xylose, p < 0.05 compared to both study groups; 49.20 +/- 1.98% for 3O MG, p < 0.05 compared to both study groups). Baseline L/R ratio was increased (0.292 +/- 0.072%, EN; 0.463 +/- 0.118%, TPN) compared with the controls (0.038 +/- 0.006%, p < 0.05 compared to both study groups). In the EN group, the L/R ratio displayed a progressive, significant fall. In the TPN group, no significant change in the L/R ratio occurred. This study demonstrates that GIT dysfunction is evident in critically ill patients and suggests that loss of GIT mucosal integrity is reversed by the institution of EN.

The effect of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability.

STUDY OBJECTIVE: To quantify simultaneously the pulmonary and gastrointestinal (GI) damage that occurs during uncomplicated surgery requiring cardiopulmonary bypass (CPB), and to examine the relationships between markers of such damage. DESIGN: Prospective, open. SETTING: Adult ICU of a national referral hospital. PATIENTS: Twenty patients undergoing elective CPB surgery. MEASUREMENTS AND RESULTS: Pulmonary vascular injury was assessed using the protein accumulation index (PAI), a double isotope technique specific for high permeability pulmonary edema. The relationships of the PAI with percent neutrophils in bronchoalveolar lavage (BAL), serum, and BAL myeloperoxidase (MPO), and bypass time were examined. Splanchnic vascular injury was assessed using tonometry to measure intramucosal pH (pHi) and the ratio of absorbed lactulose to L-rhamnose (L/R ratio) to determine gut mucosal permeability. Positive correlations were observed between bypass time and PAI (r = 0.64, p < 0.01), percent neutrophils in the postoperative BAL and PAI (r = 0.51, p < 0.05), and postoperative serum MPO and PAI (r = 0.77, p < 0.001). The L/R ratio rose significantly following CPB from 0.04 +/- 0.01 in controls to 0.48 +/- 0.05 (p < 0.0001). The L/R ratio in patients who developed a low pHi was 0.59 +/- 0.06 compared with 0.32 +/- 0.07 in those whose pHi remained normal (p < 0.05). No significant correlation between bypass time and pHi (r = -0.3, p = 0.33), bypass time and L/R ratio (r = 0.27, p = 0.26), PAI and L/R ratio (r = 0.2, p = 0.42), PAI and pHi (r = -0.34, p = 0.16), postoperative serum MPO and L/R ratio (r = 0.03, p = 0.90), or postoperative serum MPO and pHi (r = -0.10, p = 0.67) could be demonstrated. CONCLUSIONS: Pulmonary and GI injury are detectable following uncomplicated CPB. The absence of any relationship between the respective markers of dysfunction suggests that differing pathologic processes are responsible.

Exercise-induced airway narrowing in army recruits with a history of childhood asthma.

The aim of this study was to determine whether the addition of cold, dry, inspired air to maximum heart rate (MHR) exercise increased the number of subjects demonstrating abnormal airway narrowing, when applied to symptom-free army recruits with a history of asthma in childhood. One hundred recruits with a history of asthma in childhood underwent two exercise challenges to maximum heart rate, breathing either room air or cold dry air in randomized order. The percentage fall index (%FI) was calculated for each challenge, a positive result being > or = 15%. A total of 29 subjects had a positive % fall index, 12 subjects were positive to both challenges, 7 to the room air alone and 10 to the cold air challenge alone. In these subjects (n = 29), the mean (SD) % fall index to the cold air challenge was 22.7 (11.0)% compared with 16.3 (9.5)% for the room air challenge. We conclude that when employed as a screening test for abnormal airway narrowing, the addition of cold, dry, inspired air during exercise does not increase the number of subjects with a positive response, but the magnitude of the response is increased.

Pulmonary endothelial permeability in patients with severe lung injury. Clinical correlates and natural history.

STUDY OBJECTIVE: To establish the natural history of lung injury in adult respiratory distress syndrome (ARDS) in terms of increased pulmonary vascular permeability. Secondly, to relate such changes to the number of neutrophils in bronchoalveolar lavage (BAL) and a clinical score of the severity of lung injury. DESIGN: Prospective, open. SETTING: Adult intensive care unit of a tertiary (national) referral hospital. PATIENTS: Fourteen patients meeting accepted diagnostic criteria for ARDS. INTERVENTIONS: Mechanical ventilatory support. Conventional intensive care and support for other failed organ systems as appropriate. MEASUREMENTS AND RESULTS: Pulmonary vascular permeability was estimated using a dual isotope technique (protein accumulation index [PAI]), neutrophil numbers by BAL and the severity of ARDS by the lung injury score (LIS). The PAI and LIS were measured simultaneously on three occasions as far apart as possible during the course of the illness. A single BAL was performed immediately after one of the three PAI/LIS measurements, the precise timing being dictated by the clinical stability of each patient. Fourteen patients (8 male; age range, 19 to 69 years) were studied, 1.40 +/- 0.16, 11.36 +/- 1.79, and 20.90 +/- 2.30 days after the onset of ARDS (mean +/- SEM). Six patients died. The PAI (normal range, 0 to 1.0 x 10(-3)) was 2.81 +/- 0.39, 2.94 +/- 0.48, and 2.80 +/- 0.87; and LIS (severe injury > or = 2.5) was 2.18 +/- 0.25, 2.48 +/- 0.14, and 2.06 +/- 0.27, respectively. The BAL neutrophil content was 54.09 +/- 8.89. There were significant positive correlations between PAI and LIS (r = 0.73, p < 0.001) and PAI and BAL neutrophil content (r = 0.81, p < 0.001). CONCLUSIONS: These data suggest that increased pulmonary vascular permeability persists throughout the course of ARDS and is related to a clinical score of injury severity and BAL neutrophil content.

Nosocomial pneumonia in the intensive care unit.

The most important epidemiological, aetiological and diagnostic problems related to nosocomial pneumonia in the intensive care unit and its significance are reviewed. Areas of uncertainty are identified, as are methods for improving our understanding of this complex condition.

Use of continuous positive airway pressure in the management of community acquired pneumonia.

Three cases of severe community acquired pneumonia requiring ventilatory support are presented. Continuous positive airway pressure (CPAP) applied via a tightly fitting face mask was used and was successful in two cases; the third required intermittent positive pressure ventilation. More extensive use of CPAP in these circumstances should be considered.

The academic medical centre: an idea whose time has come.

Interdependence of faculties of medicine or health sciences and teaching hospitals is central to the academic medical centre's three "products": education, research and clinical service. Whether a voluntary association, partnership, joint venture or single entity, the strength of the association of member institutions must lie in mutual dependency. With the potential of reducing costs and increasing effectiveness through administrative efficiency and rationalization, especially of planning and setting priorities, the academic medical centre can outstrip its individual member institutions in contributing to the solution of Canada's present and future challenges in health care.

Leptospirosis--a cause for concern?

A severe case of Weil's disease is presented. The particular relevance of this condition to the Armed Forces and Service physicians is discussed, together with methods of diagnosis.