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Biomedical subjects

W J Sibbald

Publications and source records attributed to W J Sibbald.

At least 55 records · Page 3Linked to original sources

A systematic review of the cost-effectiveness of noncardiac transitional care units.

OBJECTIVE: To critically appraise and summarize the studies examining the cost-effectiveness of noncardiac transitional care units (TCUs). DATA SOURCES: We conducted a computerized literature search using MEDLINE, and Current Contents from January 1, 1986 to December 31, 1995 and HealthSTAR from January 1, 1989 to December 31, 1995 with the key words intermediate care unit, respiratory care unit, and step-down unit. Bibliographies of all selected articles and review articles were examined. Personal files were also reviewed. STUDY SELECTION: (1) POPULATION: patients in a noncardiac TCU of an acute-care institution; (2) intervention: addition of a noncardiac TCU to the institution; and (3) outcomes: patient outcome-survival and associated costs. DATA EXTRACTION: The necessary data were abstracted and study validity was evaluated by two independent reviewers using a modification of previously published criteria. DATA SYNTHESIS: The studies were summarized qualitatively; upon inspection, they were too heterogeneous to allow quantitative analysis. While the studies all claimed that their TCUs were cost-effective, the economic evaluation designs were flawed to such an extent that the validity of the conclusions is suspect. CONCLUSIONS: To date, the evidence in the literature is insufficient to determine under which circumstances, if any, TCUs are a cost-effective alternative technology to the traditional institution with only ICU and general ward beds.

Humans↗

The effect of positive pressure airway support on mortality and the need for intubation in cardiogenic pulmonary edema: a systematic review.

OBJECTIVE: To critically appraise and summarize the trials examining the addition of continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NPPV) to standard therapy on hospital mortality, need for endotracheal intubation, and predischarge left ventricular function in patients admitted to the hospital with cardiogenic pulmonary edema with gas exchange abnormalities. DATA SOURCES: We searched MEDLINE (1983 to June 1997) and bibliographies of all selected articles and review articles. We also reviewed the abstracts from the proceedings of relevant meetings from 1985 to 1997. STUDY SELECTION: (1) POPULATION: patients presenting to hospital with cardiogenic pulmonary edema; (2) intervention: one of the following three: (a) the use of CPAP and standard medical therapy vs standard medical therapy alone; (b) the use of NPPV and standard medical therapy vs standard medical therapy alone; and (c) the use of NPPV and standard therapy vs CPAP and standard therapy; (3) outcome: hospital survival, need for endotracheal intubation, or predischarge left ventricular dysfunction; and (4) study design: randomized controlled trial (RCT); if there were fewer than two RCTs, other study designs were included. DATA EXTRACTION: Two authors independently extracted data and evaluated the methodologic quality of the studies. DATA SYNTHESIS: CPAP was associated with a decrease in need for intubation (risk difference, -26%, 95% confidence intervals, -13 to -38%) and a trend to a decrease in hospital mortality (risk difference, -6.6%; +3 to -16%) compared with standard therapy alone. There was insufficient evidence to comment on the effectiveness of NPPV either compared with standard therapy or CPAP and standard therapy. Evidence was also lacking on the potential for either intervention to cause harm. CONCLUSIONS: A modest amount of favorable experimental evidence exists to support the use of CPAP in patients with cardiogenic pulmonary edema. CPAP appears to decrease intubation rates and data suggest a trend toward a decrease in mortality, although the potential for harm has not been excluded. The role of NPPV in this setting requires further study before it can be widely recommended.

Clinical Trials as Topic↗

Influence of sepsis on the plasma elimination pharmacokinetics of diaspirin crosslinked hemoglobin in rats.

Septic shock is characterized by abnormalities in microcirculatory O2 delivery (QO2) and profound tissue O2 debt. Administration of crosslinked hemoglobin may be a means of augmenting the QO2 and tissue O2 availability. Sepsis is associated with hemodynamic and metabolic alterations which may affect the pharmacokinetics of crosslinked hemoglobin. The objective of this study was to determine the effect of sepsis on the plasma elimination of diaspirin crosslinked hemoglobin (DCLHb). Twenty-four hours after the induction of sepsis by cecal ligation and perforation, septic (n = 9) and sham rats (n = 8) received an intravenous infusion of 300 mg of DCLHb and arterial blood samples were taken at regular intervals to determine free plasma hemoglobin concentration. DCLHb elimination in septic and sham rats was consistent with first-order elimination kinetics. The half life (t1/2) for septic rats was 4.2 +/- 0.7 h and was significantly shorter than the t1/2 of non-septic rats (5.4 +/- 0.9 h). In all rats, free plasma hemoglobin returned to basal levels by 24 hours after DCLHb administration. The volume of distribution for DCLHb in the septic and non-septic rats was not significantly different and suggests that DCLHb is not influenced by altered gut permeability. Despite significant changes in some elimination parameters the differences were small. Consequently, dosing regimens for this compound may not need to be altered in sepsis.

Animals↗

Determining the potential need for a bereavement follow-up program: how well are family and health care workers' needs currently being met?

The purpose of the study was to determine the need for a bereavement follow-up program for either the families of patients dying in a critical care unit or the health care workers who care for these patients. Two questionnaires, the first a telephone administered questionnaire to all consenting family members of patients dying in the critical care unit, and the second a self-administered questionnaire administered to all health care workers in the critical care unit, were developed and piloted for content validity and clarity. The data was analyzed using descriptive statistics. Family members of 42 patients who died in the critical care unit were interviewed (54% response rate). During the critical care unit stay most family members obtained support from family and friends. While 70% listed health care workers as a source of support, 50% were satisfied with the support from staff. After a family member had died, 40% of those interviewed did not identify a specific source for support and 48% were interested in obtaining information on community resources available for aid in the bereavement process. The results from 117 (79% response rate) health care workers revealed that 30% were either uncomfortable or only somewhat comfortable with the dying process and the support available for them to deal with the death of their patients. The authors identified a need for bereavement follow-up programs for both the families of patients who die in the critical care unit and for the health care workers who care for these patients.

Adult↗

Assessing the efficiency of the admission process to a critical care unit: does the literature allow the use of benchmarking?

OBJECTIVES: To determine the ability of the current literature to supply appropriate data for benchmarking admission practice to a multidisciplinary critical care unit. DESIGN: Retrospective review of data collected prospectively on a cohort of 614 patients and a systematic review of the literature. SETTING: A 30-bed multidisciplinary critical care unit at a university teaching hospital. PATIENTS: Consecutive admissions to the critical care unit over a 6-month period. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: For each patient, demographic data and admitting diagnosis were recorded on admission. Information necessary to calculate the Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention Scoring System (TISS) scores were collected daily. TISS variables were categorized as "active" or "non-active" treatment variables. Patients were then identified on a daily basis as receiving or not receiving active treatment. A review of the literature, using MEDLINE and the search term "Therapeutic Intervention Scoring Index" (as a textword), was conducted to identify studies that had similarly divided their patients. Using the method of benchmarking, the proportion of patients admitted who received active treatment during their stay in the critical care units was compared between the index critical care unit and those in the literature. A greater proportion of the patients admitted to our unit received active treatment (97.7%) when compared to other studies in the literature (20-66%). However, a number of potential confounding factors were present, such as the availability of intermediate care units, overnight recovery room ventilation, and critical care bed availability between the index critical care unit and those described in the literature. CONCLUSIONS: The current literature does not provide adequate data on critical care unit admission practices to allow useful application of the method of benchmarking. There is a need for publicly accessible large databases to allow individual critical care units to determine their level of efficiency when compared to similar institutions.

APACHE↗

Critical care in Canada. The North American difference.

Critical care medicine in Canada has evolved into a multidisciplinary service, teaching, and research activity. Pressure on existing funding models for the delivery of health care in Canada is leading to substantial change in the hospital sector. Although not explicitly targeted for change, pre-existing models of critical care delivery will be caught in the acute care services, redesign (that results from the health care restructuring because of the substantial impact that delivering critical care services has on overall hospital budgets). Although starting from different perspectives, the Canadian and American health care systems seem to be converging in their health care redesign principles, with themes such as integration, regionalization, physician payment reform, health care worker redesign, and global budgeting common through the multiplicity of plans being articulated. What critical care will look like in its major domains (service, education, and research) in the year 2001 is difficult to foresee at this time. In this context, therefore, change occurring in Canada's critical care system will be no less challenging than what will occur in the United States or other health care systems. For the resources we have developed for the critically ill patient population to survive health care redesign, we must improve our way of working together internationally, to understand and benchmark best practices and to share ideas for the most effective critical care systems.

Aged↗

Consensus conferences in critical care medicine. Methodologies and impact.

Consensus conferences for the purposes of producing practice guidelines are occurring with increasing frequency both nationally and internationally. The international collaboration of national sciences in these efforts could have a dramatic impact on international standards of care. Too little emphasis is given to conference evaluations in terms of validity of methods, quality of recommendations, and influence on clinical practice and patient outcome. This article provides an overview of consensus methods used to produce guidelines in critical care. It also discusses the strengths and weaknesses of these methods, and how these may influence consensus guidelines. Finally, a brief overview of theoretically sound methods that can serve as benchmarks to evaluate current methods, and the bases for the development of improved methods is provided.

Consensus Statements as Topic↗

Myocardial collagen changes and edema in rats with hyperdynamic sepsis.

OBJECTIVE: To determine if sepsis, which is accompanied by both systolic and diastolic myocardial dysfunction, involves changes in myocardial collagen, as myocardial collagen changes can affect both myocardial compliance and contractility. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory at a university-affiliated hospital. SUBJECTS: Male Sprague-Dawley rats, weighing 310 to 396 g. INTERVENTIONS: Cecal ligation and perforation (to induce sepsis) for 24 (n = 9) or 48 hrs (n = 9); sham laparotomy for 24 (n = 10) or 48 hrs (n = 9) with saline fluid resuscitation or normal control (n = 5) groups. MEASUREMENTS AND MAIN RESULTS: Collagen content and interstitial space were determined, using polarized light microscopy and a computer video densitometry system. At 24 and 48 hrs post surgery, heart rate and cardiac index were increased, and systemic vascular resistance index was decreased significantly in the sepsis vs. the sham rats. Collagen content was decreased significantly in the sepsis vs. the sham groups both at 24 and 48 hrs following surgery (1.83 +/- 0.79 [SD] % [24 hrs], 1.76 +/- 0.31% [48 hrs] vs. 2.83 +/- 0.73% [24 hrs], 2.25 +/- 0.72% [48 hrs]; p < .01). Interstitial space was increased significantly in the sepsis vs. the sham groups (13.9 +/- 3.5% [24 hrs], 15.6 +/- 5.2% [48 hrs] vs. 8.6 +/- 4.2% [24 hrs], 9.9 +/- 4.8% [48 hrs]; p < .01). CONCLUSIONS: Sepsis is accompanied by changes in myocardial collagen content and myocardial edema. These changes may contribute to the systolic and diastolic myocardial dysfunction, and particularly to the ventricular dilation, observed in sepsis.

Animals↗

Transfusing red blood cells stored in citrate phosphate dextrose adenine-1 for 28 days fails to improve tissue oxygenation in rats.

OBJECTIVE: To determine whether the time that red blood cells are stored in citrate phosphate dextrose adenine-1 solution before transfusion alters the ability to improve tissue oxygenation. DESIGN: Prospective, randomized, controlled study. SETTING: University research institute laboratory. SUBJECTS: Male Sprague-Dawley rats (350 to 450 g). INTERVENTIONS: Twenty-four hours after randomization to sham laparotomy (n = 21) or cecal ligation and perforation (n = 16)1 supply-dependency of systemic oxygen uptake (VO2) was induced in rats by isovolemic hemodilution. Rats were then re-randomized to receive either rat red blood cells stored in citrate phosphate dextrose adenine-1 for 3 days ("fresh" n = 17) or rat red blood cells stored in citrate phosphate dextrose adenine-1 for 28 days ("old" n = 20). MEASUREMENTS AND MAIN RESULTS: Changes in systemic VO2 were measured for 90 mins to determine the efficiacy of the treatment. Statistical analysis included a fully factorial repeated-measures, generalized linear model. No significant interaction was found between cecal ligation and perforation or sham animals and transfusion with fresh or old red blood cells. However, comparing the combined groups of animals receiving either fresh or old red blood cells, we found that after the transfusion of old red blood cells, systemic VO2 was not significantly improved (after hemodilution 1.68 +/- 0.27 mL/100 g/min, after transfusion 1.86 +/- 0.17 mL/100 g/min; p > .05). In contrast, transfusion with fresh red blood cells acutely increased systemic VO2 (after hemodilution 1.62 +/- 0.06 mL/100 g/min, after transfusion 2.10 +/- 0.09 mL/100 g/min; p = .049). CONCLUSION: Storage of rat red blood cells for 28 days in citrate phosphate dextrose adenine-1 impaired their ability to improve tissue oxygenation when transfused into either control or septic rats placed into supply dependency of systemic VO2.

Adenine↗

A retrospective review of a large cohort of patients undergoing the process of withholding or withdrawal of life support.

OBJECTIVES: To determine the proportion of patients who died as a result of the withdrawal or withholding of life support (WD/WHLS) in the intensive care units (ICUs) of three teaching hospitals and to describe the process involved by determining: a) why the decision was made to withdraw support (WDLS); b) when WDLS took place; and c) how the WDLS process was conducted. DESIGN: Retrospective cohort study. SETTING: Three university-affiliated ICUs. PATIENTS: Four hundred nineteen patients who died in one of three academic, tertiary care ICUs over a 1-yr period. INTERVENTIONS: Retrospective chart review. Data collected included age, gender, admitting diagnoses, comorbid disease, Acute Physiology and Chronic Health Evaluation II score, and mode of death (brain death, death due to withholding of life support, death due to WDLS, or death despite ongoing therapy). For those patients dying due to WDLS, the reason for WDLS, person initiating discussion, timing of WDLS, degree of organ dysfunction, order of withdrawal of life support modalities, and the use of sedatives and analgesics were recorded. MEASUREMENTS AND MAIN RESULTS: Seventy percent of patients died by WD/WHLS and 8.4% were brain dead. Patients undergoing WD/WHLS were older and had a longer length of stay than patients dying from other causes. Poor prognosis was the most common reason given for WDLS, reflected by significant organ dysfunction at the time of WDLS. Future quality of life was a less frequently cited reason. Most patients undergoing WDLS did so early in their ICU stay, although time to WDLS appeared to reflect diagnostic group. Few meetings occurred before WDLS and death occurred soon after initiating WDLS. There was a preference of withdrawing mechanical ventilation last and large amounts of morphine (mean 21 +/- 33 [SD] mg/hr) and benzodiazepines (mean 8.6 +/- 11 mg/hr) were used. Little variability in practice was apparent among the studied ICUs. CONCLUSIONS: Similar to other studies, WD/WHLS was the most common cause of death in academic ICUs and poor patient prognosis was considered the most important factor in deciding on WDLS. However, in contrast to other studies, future quality of life was not as frequently cited a reason for WDLS and larger amounts of morphine were used during WDLS. These discrepancies suggest areas for potential future research.

APACHE↗

Effect of noninvasive positive pressure ventilation on mortality in patients admitted with acute respiratory failure: a meta-analysis.

OBJECTIVE: To critically appraise and summarize the trials examining the addition of noninvasive positive pressure ventilation to standard therapy on hospital mortality and need for endotracheal intubation in patients admitted with acute respiratory failure. DATA SOURCES: We searched MEDLINE (1966 to September 1995) and key references were searched forward using the Scientific Citation Index (SCISEARCH). Bibliographies of all selected articles and review articles were examined. Authors of all selected and review articles were contacted by letter to identify unpublished work. STUDY SELECTION: a) POPULATION: patients with acute respiratory failure; b) intervention: noninvasive positive pressure ventilation; c) outcome: mortality and/or endotracheal intubation; and d) design: randomized, controlled study. Two of us independently selected the articles for inclusion; disagreements were settled by consensus. Seven (three unpublished) of 212 initially identified studies were selected. DATA EXTRACTION: Two authors independently extracted data and evaluated methodologic quality of the studies. DATA SYNTHESIS: Noninvasive positive pressure ventilation was associated with decreased mortality (odds ratio = 0.29; 95% confidence interval 0.15 to 0.59) and a decreased need for endotracheal intubation (odds ratio = 0.20; 95% confidence interval 0.11 to 0.36). Sensitivity analysis suggested a greater benefit of noninvasive positive pressure ventilation in patients with chronic obstructive pulmonary disease (COPD). The inclusion/exclusion of unpublished trials did not influence these results. CONCLUSIONS: The addition of noninvasive positive pressure ventilation to standard therapy in patients with acute respiratory failure improves survival and decreases the need for endotracheal intubation. However, this effect is restricted to patients whose cause of acute respiratory failure is an exacerbation of COPD. Further research is warranted to determine whether noninvasive positive pressure ventilation confers benefit in patients without COPD who have acute respiratory failure.

Acute Disease↗

Polymyxin-dextran antiendotoxin pretreatment in an ovine model of normotensive sepsis.

OBJECTIVE: To test the hypothesis that adult sheep pretreated with polymyxin-dextran and then made septic by cecal ligation and perforation would have fewer changes in microvascular integrity and cellular architecture in extrapulmonary organs. DESIGN: Prospective, randomized, double-blind, placebo-controlled animal study. SETTING: An animal research facility in a university-affiliated hospital. SUBJECTS: Mature, male Suffolk sheep (32 to 67 kg). INTERVENTIONS: Animals with chronic indwelling catheters were pretreated with polymyxin B-dextran (6 mg/kg) or placebo (dextran) and an intra-abdominal focus of infection was then produced by cecal ligation and perforation. Treatment (polymyxin B or placebo) was continued every 8 hrs for 48 hrs. MEASUREMENTS AND MAIN RESULTS: Forty-eight hours after randomization, the polymyxin B-dextran group manifested significantly less pyrexia (p = .04), higher mean arterial pressures (p = .02), less variable serum albumin concentrations (p = .05), and a trend toward decreased lactate concentrations (p = .10). Qualitative morphometry and semiquantitative scoring of tissue from gastrocnemius muscle demonstrated that polymyxin B-dextran-treated sheep had significantly increased total capillary (p = .04) and capillary luminal areas (p = .038) and less mitochondrial swelling and damage (p = .03) compared with the placebo sheep. CONCLUSIONS: Pretreatment of sheep in a polymicrobial, peritonitis model of sepsis with polymyxin B-dextran resulted in a significant amelioration of sepsis-induced ultrastructural damage. In placebo-treated control animals, these ultrastructural lesions were associated with a greater severity of sepsis, as measured by the presence of pyrexia, increased lactate concentrations, and less stable blood pressures. These findings justify the investigation of the effects of polymyxin B-dextran in a post onset model of sepsis.

Animals↗

Diaspirin crosslinked hemoglobin improves systemic oxygen uptake in oxygen supply-dependent septic rats.

Diaspirin crosslinked hemoglobin (DCLHb) is a cell-free hemoglobin derived from human erythrocytes. DCLHb has been shown to improve blood flow to vital organs in healthy and septic animals. In this study, we determined the efficacy of DCLHb by comparing its effect on systemic O2 uptake to freshly stored and aged red blood cells (RBCs) in septic rats. Twenty-four hours after induction of sepsis by cecal ligation and perforation, O2 supply dependency was created by isovolemic hemodilution with rat plasma. In O2 supply dependency, rats were randomized to receive an exchange transfusion of 7.5 ml "fresh" RBCs (stored < 6 d; Hct: 70%), "fresh" diluted RBCs (stored < 6 d; Hct: 30%), "old" RBCs (stored 28 to 35 d; Hct: 70%), or DCLHb (Hb: 100 g/L). We found, that survival following O2 supply dependency and transfusion with old RBCs was poor (33% versus 91.7% in the other groups; p < 0.01), precluding further analysis of post-transfusion data from this group. Systemic O2 uptake increased in all remaining groups (p < 0.001), while systemic O2 delivery increased with "fresh" RBCs (p < 0.0001) and "fresh" diluted RBCs (p < 0.05) but not with DCLHb. Systemic O2 extraction increased with DCLHb as compared to baseline (p < 0.05) and to the other groups (p < 0.0001). Improved tissue oxygenation was associated with an increase in blood pressure and a fall in arterial lactate in all groups. We conclude that transfusion of DCLHb or "fresh" RBCs was efficacious at increasing systemic O2 uptake in O2 supply-dependent, septic rats.

Animals↗

Structure-function relationships in the septic rat heart.

Myocardial edema and histologic changes consistent with tissue injury are reported in association with sepsis-induced myocardial depression. The objective of the present study was to determine whether, in the absence of shock, such changes (assessed by studying microvascular albumin flux, tissue edema, and morphometry) are prerequisites for the development of contractile dysfunction in sepsis. Sprague-Dawley rats were randomized into groups for either cecal ligation and perforation (CLP) or sham study. Twenty-four hours after entry of animals into the study, their myocardial function was assessed with the Langendorff isolated heart technique. Left-ventricular developed pressure (preload: 5 mm Hg) was reduced in CLP animals (34.9 +/- 3.3 mm Hg, n = 10) as compared with time-matched controls (46.4 +/- 4.0 mm Hg, n = 8, p < 0.05, unpaired t test). This was associated with a significant reduction in the maximal rate of increase (+ dP/dt(max)) and decrease (-dP/dt(max)) in left ventricular pressure in the CLP group (sham versus CLP, unpaired t test, p < 0.05). Upon reperfusion, after 30 min of ischemia, left ventricular resting tension was decreased in CLP as compared with sham-treated animals (sham versus CLP, analysis of variance (ANOVA) with repeated measures, p < 0.05). At 24 h, sepsis was not associated with myocardial edema (wet:dry weight ratio, sham = 4.094 +/- 0.098, n = 10; CLP = 4.185 +/- 0.066, n = 7), and tissue albumin flux was reduced (sham = 194 +/- 27 microliters. h-1. g dry wt-1, n = 10; CLP = 100 +/- 14 microliters. h-1. g dry wt-1, n = 7). In tissue processed for electron microscopy, we found no evidence of tissue injury or edema at either 24 or 48 h after CLP. We conclude that polymicrobial normotensive sepsis causes myocardial contractile depression in the absence of changes in myocardial structure.

Animals↗

Animal models for blood transfusion: a model for sterile blood sampling in the rat.

Rat blood is frequently used for experimental transfusion. However, no data are available concerning the quality of the blood used, although bacterial contamination could severely alter results. To obtain large quantities of sterile rat blood for a transfusion study, we tested carotid artery cannulation, known as a standard procedure. Blood cultures from the collected blood showed polymicrobial overgrowth even after sterility measures were improved. In contrast, the puncture of the abdominal aorta proved to be a simple and reliable method for the collection of sterile blood. We conclude that studies using blood collected from donor rats should be controlled and the quality of such blood be tested before transfusion.

Animals↗

Decreased capillary density in vivo in bowel mucosa of rats with normotensive sepsis.

Translocation of bacteria and endotoxin leading to sepsis occurs in animals subjected to burns or intestinal ischemia. This may be mediated in part by bowel mucosal microcirculatory dysfunction. However, the direct effect of sepsis on the mucosal microcirculation is unknown. The objective of this study was to develop a technique for intravital microscopy of the mucosa of the small bowel in an animal model of normotensive sepsis. We tested the hypothesis that normotensive sepsis induced by cecal ligation and perforation leads to a decrease in perfused capillaries in the small bowel mucosa at 24 hr. Twelve male Sprague-Dawley rats were hemodynamically monitored and randomly assigned to cecal ligation and perforation (CLP) or control laparotomy (sham). Twenty-four hours after initial surgery each animal was reanesthetized and the mucosal surface of the distal small bowel prepared for intravital microscopy. Laser doppler measurements of bowel wall blood flow were made immediately and repeated after a 30-min stabilization period. Intravital microscopy of the mucosal microcirculation of six villi per animal was performed and the images recorded on videotape (2 min/villus). The areas surrounded by perfused capillaries (intercapillary area) were then measured using video analysis software. Laser doppler flowmetry revealed a decrease in bowel wall blood flow during the stabilization period in the shams that did not occur in the CLP rats. The intercapillary areas were significantly greater in the CLP rats compared to sham rats (1329 +/- 316 microns2 vs 979 +/- 217 microns2, P = 0.044). The intercapillary areas were also more highly variable in the CLP group (median coefficient of variation 102 vs 83% in the sham group, P = 0.025). Intravital microscopy may be used to examine microcirculatory function of the small bowel mucosa. Sepsis induced by CLP leads to a decrease in the number of perfused capillaries in the small bowel mucosa.

Animals↗