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Biomedical subjects

W J Sibbald

Publications and source records attributed to W J Sibbald.

At least 127 records · Page 7Linked to original sources
PubMed1988

Ibuprofen reduces the progression of permeability edema in an animal model of hyperdynamic sepsis.

Since severity of acute lung injury (ALI) is reduced by pretreatment with non-steroidal agents, we hypothesized that ibuprofen would ameliorate ALI when administered after the onset of septic lung injury. Twenty-four hours after cecal ligation and perforation (CLP) in 23 sheep during a 4 h study period (period S), pulmonary lymph flow (QL) increased 16.2 +/- 12.1 ml/min (P less than 0.01) from base line, whereas lymph-to-plasma total protein concentration ratios ([L/P]TP) remained unchanged. During the subsequent 24 h of study (period D), 10 sheep received parenteral ibuprofen, 12.5 mg/kg every 6 h, and 13 sheep served as untreated septic controls. Throughout period D, a progressive increase in QL (16.2 +/- 16.3 ml/60 min) from period S was greater in the untreated than in the ibuprofen (2.5 +/- 9.0 ml/60 min, P less than 0.02) group. Between base line and period D, increase in lung wet-to-dry weight ratios was greater in the untreated group than in the ibuprofen group (P less than 0.05). Concurrently mean pulmonary arterial pressure increased 4.7 +/- 7.3 mmHg in the untreated group (P less than 0.05) during period D vs. 0.0 +/- 5.2 mmHg in the ibuprofen group (NS). When administered after septic ALI had been established by CLP, ibuprofen reduced an otherwise progressive increase in both fluid flux and extravascular lung water.

Animals↗
PubMed1988

Effect of dobutamine on lung microvascular fluid flux in sheep with "sepsis syndrome".

The effect on pulmonary fluid balance of adrenergic receptor agonist agents commonly employed in clinical sepsis has not been well characterized. Therefore, we tested the hypothesis that dobutamine would increase pulmonary microvasular fluid flux in experimental sepsis-induced lung injury. To define the effects of this synthetic catecholamine on pulmonary lymph flow (QL), we infused dobutamine in sheep at two doses in sequence (5 micrograms/kg/min and 10 micrograms/kg/min) before and after the induction of intraperitoneal sepsis which resulted in the development of lung microvascular injury. In the nonseptic state, cardiac output increased at both 5 micrograms/kg/min and 10 micrograms/kg/min (22 and 36 percent, respectively), while QL was unchanged from baseline (for 5 micrograms, delta QL = +0.44 +/- 1.35 ml/15 min; not significant) (for 10 micrograms, delta QL = -0.20 +/- 1.0 ml/15 min; not significant). Values for the ratio of lymph/plasma total protein levels [( L/P]TP) fell modestly in the nonseptic study at both doses (p less than 0.05). With established sepsis syndrome, QL increased from the nonseptic baseline study (2.99 +/- 1.8 to 7.01 +/- 3.95 ml/15 min; p less than 0.05), without change in [L/P]TP ratios or the calculated microvascular hydrostatic pressure. (Pmv) During sepsis, dobutamine infusion was again associated with an increase in cardiac output at both the 5 micrograms/kg/min (+29 percent) and 10 micrograms/kg/min (+33 percent) doses, while QL increased modestly only with the lower dose of dobutamine infused (5 micrograms/kg/min, delta QL = 1.80 +/- 2.2 ml/15 min; p less than 0.05). In this model of sepsis-induced lung injury, dobutamine increased systemic flow without substantially augmenting QL.

Animals↗
PubMed1988

The effects of coronary artery disease on cardiac function in nonhypotensive sepsis.

To assess the effects of coronary artery disease on cardiac function in the presence of sepsis, we compared several hemodynamic indices in two groups of septic patients. Group 1 (n = 69) consisted of patients with nonhypotensive sepsis without coronary artery disease. Group 2 (n = 25) comprised septic patients who had clinical evidence of coronary artery disease. All patients were hemodynamically stable and normotensive at the time of the study. None required inotropic support. While the two groups had similar mean heart rates, mean blood pressures, and biventricular filling pressures, the mean cardiac index was significantly lower in group 2 (3.5 +/- 0.9 L/min/m2 vs 4.4 +/- 1.2; p less than 0.05). This lower cardiac index was related to significantly lower end-diastolic volume indices in group #2, not to differences in contractility between groups. Since the ventricular filling pressures of the groups were similar, the differences in end-diastolic volumes indicate differences in the biventricular compliance. In the presence of hyperdynamic, nonhypotensive sepsis, coronary artery disease was associated with a clinically significant impairment of biventricular compliance, which resulted in a reduction in cardiac output and systemic oxygen transport.

Aged↗
PubMed1987

High-dose corticosteroids in patients with the adult respiratory distress syndrome.

Corticosteroids are widely used as therapy for the adult respiratory distress syndrome (ARDS) without proof of efficacy. We conducted a prospective, randomized, double-blind, placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia, diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization. The causes of ARDS included sepsis (27 percent), aspiration pneumonia (18 percent), pancreatitis (4 percent), shock (2 percent), fat emboli (1 percent), and miscellaneous causes or more than one cause (42 percent). Fifty patients received methylprednisolone (30 mg per kilogram of body weight every six hours for 24 hours), and 49 received placebo according to the same schedule. Serial measurements were made of pulmonary shunting, the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen, the chest radiograph severity score, total thoracic compliance, and pulmonary-artery pressure. We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry. Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality (respectively, 30 of 50 [60 percent; 95 percent confidence interval, 46 to 74] and 31 of 49 [63 percent; 95 percent confidence interval, 49 to 77]; P = 0.74) or in the reversal of ARDS (18 of 50 [36 percent] vs. 19 of 49 [39 percent]; P = 0.77). However, the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment. Infectious complications were similar in the methylprednisolone group (8 of 50 [16 percent]) and the placebo group (5 of 49 [10 percent]; P = 0.60). Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome.

Clinical Trials as Topic↗
PubMed1986

Hemodynamic adaptation to acute myocardial contusion complicating blunt chest injury.

The immediate hemodynamic sequelae of blunt chest injury complicated by acute myocardial contusion were examined in multiply traumatized patients. Focal defects of ventricular wall motion defined by gated cardiac scintigraphy identified acute myocardial contusion in 28 of 43 patients, involving the right ventricle alone in 18 (group 1A), the left ventricle in 4 (group 1B) and both ventricles in 6 (group 1C). Qualitatively normal ventricular wall motion was found in the 15 patients (group 2). Although there was no difference between groups 1A and 2 in mean systemic oxygen transport (620 +/- 189 vs 627 +/- 105 ml/min/m2), left ventricular ejection fraction (52 +/- 14% vs 60 +/- 9%) or calculated left ventricular end-diastolic and end-diastolic and end-systolic volumes, mean right ventricular (RV) ejection fraction was significantly lower in group 1A (29 +/- 9%) than in group 2 (47 +/- 7%, p less than 0.01). Concomitantly, evidence of RV systolic dysfunction was ml/m2) but not in group 2 (RV end-systolic volume, 50 +/- 21 ml/m2, p less than 0.05). RV stroke work was similar between the groups, and RV pump function was identical by virtue of a larger RV preload in group 1A (RV end-diastolic volume 143 +/- 63 ml/m2) than in group 2 (RV end-diastolic volume 93 +/- 26 ml/m2, p less than 0.05). Thus, use of the RV Frank-Starling mechanism in patients with traumatic RV contusion maintains RV pump function at a level similar to that in traumatized patients without acute myocardial contusion.

Adaptation, Physiological↗
PubMed1986

Right and left ventricular performance in acute hypoxemic respiratory failure.

We examined biventricular performance on two occasions in 28 patients with acute hypoxemic respiratory failure (ARF), using a combination of invasively determined pressures and flows as well as radionuclide scintigraphy to measure the right and left ventricular ejection fractions (RVEF and LVEF, respectively). From the EF and concurrently measured thermodilution stroke volumes, we calculated right and left ventricular end-diastolic and end-systolic volume indices (EDVI and ESVI, respectively). Regression analysis demonstrated that changes (delta) in global right ventricular function (RVEF) were inversely correlated with concurrent changes in the mean pulmonary arterial pressure (MPAP): delta RVEF = 0.015-0.015 delta MPAP (r2 = 0.60; p less than .005), while an increase in right ventricular preload (RVEDVI) was positively correlated with changes in MPAP: delta RVEDVI = 2.68 +/- 6.27 delta MPAP (r2 = 0.46; p less than .005). Global left ventricular function (LVEF) was related to changes in systemic pressures as well as to right-sided events: delta LVEF = -0.01-0.0015(delta RVESVI) + 0.001(delta BP systolic)-0.42(CVP/RVEDVI) (r2 = 0.35; p less than .01). These data confirm the significant influence of right ventricular afterload on RVEF in ARF patients and an apparent interrelationship between altered right ventricular systolic function and global left ventricular performance.

Acute Disease↗
PubMed1986

Critically ill polyneuropathy: electrophysiological studies and differentiation from Guillain-Barré syndrome.

A polyneuropathy of varying severity has been observed in association with sepsis and critical illness in 15 patients. Since clinical evaluation is often difficult, electrophysiological studies provided definitive evidence for polyneuropathy. These revealed reductions in the amplitudes of compound muscle and sensory nerve action potentials, the most marked abnormality. Near-nerve recordings confirmed such reductions for sensory fibres. Needle electromyography revealed signs of denervation of limb muscles. Phrenic nerve conduction and needle electromyographic studies of chest wall muscles suggested that the polyneuropathy partially explained difficulties in weaning patients from the ventilator, an early clinical sign. No defect in neuromuscular transmission was demonstrated, despite the use of aminoglycoside antibiotics in some patients. In those who survived the critical illness, clinical and electrophysiological improvement occurred. The 15 critically ill polyneuropathy patients were compared with 16 Guillain-Barré syndrome patients observed during the same period. The analysis showed that the two polyneuropathies are likely to be separate entities that can be distinguished in most instances by the predisposing illness, electrophysiological features and cerebrospinal fluid results.

Aged↗
PubMed1986

Abnormal neutrophil-pulmonary interaction in the adult respiratory distress syndrome. Qualitative and quantitative assessment of pulmonary neutrophil kinetics in humans with in vivo 111indium neutrophil scintigraphy.

In the absence of direct toxins, the majority of evidence from animal models suggests that neutrophils (PMN) are necessary for the full expression of the abnormal pulmonary permeability accompanying acute microvascular lung injury. We therefore studied the role of the PMN in the human correlate of this disease, the adult respiratory distress syndrome (ARDS), by assessing the pulmonary retention of infused autologous 111Indium-labeled PMN (PMN-In). We evaluated 79 patients, prospectively categorized as: "active" ARDS (Aa; n = 30), "active" ARDS and concurrent corticosteroid therapy (As; n = 11), "resolving" ARDS (Ar; n = 13), sepsis without pulmonary edema (S; n = 7), and cardiac pulmonary edema (C; n = 18). This clinical separation was confirmed by retrospective analysis of associated measures of hemodynamic and respiratory dysfunction. We found that both analog scintigrams (positive/negative for diffuse pulmonary PMN-In sequestration) and computer-assisted quantitative analysis in 46 patients (T 1/2 of first hour demargination and percentage of peak activity/pixel/second remaining at 17 to 20 h) showed a significant rank order decrease in the pulmonary retention of labeled PMN-In through the Groups Aa----As----S----Ar----C. Our findings recognized aspects of in vivo PMN-In behavior that implied pathophysiologic differences between groups of critically ill patients in either the PMN themselves or in PMN-pulmonary endothelial interaction. This demonstrates the possibility of abnormal in vivo PMN-endothelial interaction in ARDS by virtue of the greater pulmonary localization of PMN in active ARDS versus resolving disease, septic non-ARDS states, and cardiac pulmonary edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Lack of significant long-term sequelae following traumatic myocardial contusion.

We assessed the possibility of long-term functional cardiac sequelae in patients who had sustained a traumatic myocardial contusion (group 1) by comparing this group with a cohort group of patients with similar traumatic injuries but exclusive of the cardiac component (group 2). More than one year following injury, patients in group 1 were qualitatively indistinguishable from patients in group 2 according to the New York Heart Association classification. Both the left and the right ventricular ejection fractions, less in group 1 than in group 2 immediately following trauma, were similar between groups during follow-up study at rest. During exercise to maximal work load at follow-up, changes in the mean right and left ventricular ejection fractions were also similar between the two patient groups. We therefore concluded that traumatic myocardial contusion to the left and/or right ventricle almost always resolves without significant functional sequelae within one year of injury.

Adolescent↗
PubMed1986

Pulmonary microvascular fluid flux in a large animal model of sepsis: evidence for increased pulmonary endothelial permeability accompanying surgically induced peritonitis in sheep.

To characterize some of the remote effects of systemic sepsis on the lung, we evaluated changes in pulmonary microvascular fluid flux before and during sepsis secondary to a peritoneal focus of inflammation in sheep. We induced peritonitis by cecal ligation, perforation, and devascularization. During a subsequent 72-hour study period, both the mean blood pressure and the pulmonary capillary wedge pressure were unchanged, while the cardiac index increased slightly. The PaO2 fell by 48 hours (98 +/- 8 to 84 +/- 10 mm Hg; p less than 0.05) (mean +/- SD) and subsequently remained low throughout the experiment. Simultaneously, pulmonary lymph flow increased by 24 hours (11.5 +/- 4.9 to 26.7 +/- 13 ml/hr; p less than 0.05) and remained elevated throughout the experiment while [L/P] total protein ratios remained unchanged at 24 hours (baseline: 0.59 +/- 0.15 at 24 hours: 0.65 +/- 0.16). Morphologic examination of the lung showed that this model of peritonitis was characterized by neutrophil emigration into the pulmonary interstitium by 24 hours and interstitial edema by 48 hours. Therefore this model of bacterial peritonitis in sheep demonstrates that one of the remote effects of surgically induced systemic sepsis is an increase in permeability of the pulmonary microvascular membrane.

Animals↗
PubMed1985

Heart injury in head-injured adolescents.

Of 19 adolescents (ages 10-18) admitted consecutively because of major blunt-impact trauma, 15 had head injuries (Glasgow coma scales 4-15). Eight had cardiac injury (42%), as demonstrated by cardiac wall-motion studies utilizing ECG-gated radionuclide angiography. Of the head-injured patients, 7 had cardiac injury (47%), and of these, one died in cardiac shock. Significant cardiac injury is known both experimentally and clinically to escape detection by conventional methods and a compromised cardiac output may bode ill for a damaged brain if cerebral perfusion pressure is in jeopardy.

Adolescent↗
PubMed1985

Pulmonary artery catheter infections. A prospective study.

Despite the widespread use of the Swan-Ganz pulmonary artery catheter, the incidence of catheter tip infection is not well-established. One-hundred and seventy catheter insertions in 113 patients were examined in this prospective study. Using a semiquantitative culture technique, the incidence of positive catheter tip cultures was 5.8%. No significant risk factors for catheter infection were identified, although there was a trend toward more frequent infection in patients not receiving antibiotics (p less than 0.06). Catheter tip infection appeared to result most frequently from a distant focus of infection. Although the overall incidence of positive blood cultures was significantly higher in the positive vs. negative catheter tip groups (37.9% vs. 10.6%, p less than 0.001), blood cultures were generally not a reliable guide to the presence of a catheter tip infection. We conclude that catheter infection can be contained at an acceptable level by following a reasonable protocol for catheter management.

Anti-Bacterial Agents↗