Role of Serial Phlebotomy in the Management of Blunt Solid Organ Injury in Adults.

BACKGROUND: The management of blunt spleen and liver trauma has become increasingly nonoperative. There is no consensus on timing or duration of serial hemoglobin and hematocrit monitoring in this patient population. OBJECTIVE: This study examined the clinical utility of serial hemoglobin and hematocrit monitoring. We hypothesized that most interventions occur early in the hospital course, based on hemodynamic instability or physical examination findings rather than serial monitoring. METHODS: We conducted a retrospective cohort study of adult trauma patients with blunt spleen or liver injury from November 2014 through June 2019 at our Level II trauma center. Interventions were classified as no intervention, surgical intervention, angioembolization, or packed red blood cell transfusion. Demographics, length of stay, total blood draws, laboratory values, and clinical triggers preceding intervention were reviewed. RESULTS: A total of 143 patients were studied, of whom 73 (51%) received no intervention, 47 (33%) received an intervention within 4 hr of presentation, and 23 (16%) had interventions beyond 4 hr. Of these 23 patients, 13 received an intervention based on phlebotomy results alone. Most of these patients (n = 12, 92%) received blood transfusion without further intervention. Only one patient underwent operative intervention based on serial hemoglobin results on hospital day 2. CONCLUSION: The majority of patients with these injury patterns either require no intervention or declare themselves promptly after arrival. Serial phlebotomy after initial triage and intervention may add little value in the management of blunt solid organ injury.

Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential.

Lethal infections are associated with cellular dysfunction as evidenced by a decrease in the resting transmembrane potential difference (Em) of skeletal muscle fibers. Endotoxin stimulation of macrophages evokes production of cachectin, a protein that has been implicated as a mediator of the lethal effects of endotoxemia. In the present study, rat skeletal muscle fiber Em decreased when incubated with recombinant human cachectin. The reduction of Em induced by cachectin occurred in a dose-related fashion and was inhibited by mAb against the monokine. Infusion of cachectin induced a decline of skeletal muscle Em in vivo, and suggests that cachectin may acutely mediate alterations of skeletal muscle membrane function after infection.

The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans.

The in vivo alterations in organ-specific substrate processing and endogenous mediator production induced by endotoxin were investigated in healthy volunteers. An endotoxin bolus (20 U/kg) produced increased energy expenditure, hyperglycemia, hypoaminoacidemia, and an increase in circulating free fatty acids. These changes included increased peripheral lactate and free fatty acid output, along with increased peripheral uptake of glucose. Coordinately, there were increased splanchnic uptake of oxygen, lactate, amino acids, and free fatty acids, and increased splanchnic glucose output. There were no changes in circulating glucagon, or insulin and transient changes in epinephrine and cortisol were insufficient to explain the metabolic changes. Plasma cachectin levels peaked 90 min after the endotoxin infusion, and hepatic venous (HV) cachectin levels (peak 250 +/- 50 pg/ml) were consistently higher than arterial levels (peak 130 +/- 30 pg/ml, P less than 0.05 vs. HV). No interleukin 1 alpha or 1 beta was detected in the circulation. Circulating interleukin 6, measured by B.9 hybridoma proliferation, peaked 2 h after the endotoxin challenge (arterial, 16 +/- 2 U/ml; HV, 21 +/- 3 U/ml). The net cachectin efflux (approximately 7 micrograms) from the splanchnic organs demonstrates that these tissues are a major site for production of this cytokine. Hence, splanchnic tissues are likely influenced in a paracrine fashion by regional cachectin production and may also serve as a significant source for systemic appearance of this cytokine.

Recombinant activated protein C induces dose-dependent changes in inflammatory mediators, tissue damage, and apoptosis in in vivo rat model of sepsis.

BACKGROUND: Sepsis is the tenth leading cause of death in the U.S. and creates a $16.7 billion burden on the healthcare system every year. Sepsis is characterized by a severe uncontrolled inflammatory response to the infection. Various cells and mediators are activated, and the result is a complex interaction between the inflammation and coagulation cascades leading to capillary leakage and end-organ ischemia. Current therapeutic strategies, such as recombinant human activated protein C, focus on this interplay. However, this drug's precise mechanism of action is not well understood. The aim of this study was to assess cytokine production, tissue damage, and apoptosis in a rat model of sepsis in response to various doses of this drug. METHODS: Sprague-Dawley rats were divided into eight groups, including negative control, sham, sepsis only, and five treatment groups. The sepsis and treatment groups were given Escherichia coli. Each of the treatment groups received a different dose of recombinant activated protein C to complete 30-min or 270-min infusion times from the onset of sepsis. Serum and tissue samples were collected. Interleukin (IL)-6 concentrations were measured, and serum malondialdehyde (MDA) concentrations were determined to assess generalized tissue damage. Apoptosis in the lung was evaluated using a semi-quantitative ligation-mediated polymerase chain reaction assay. RESULTS: The physiologic effects of recombinant activated protein C are dose dependent and determined by the duration of infusion. Higher doses of the drug were associated with less inflammation, apoptosis, and generalized tissue damage. Sepsis increased the mean concentration of MDA (2.1 vs. 10.9 pmol/mg of protein) and IL-6 (0 vs. 10,763 pg/mL) compared with sham-treated animals, as well as the magnitude of apoptosis in lung (2,037 vs. 8,709 pixels) (all p < 0.05). Infusion of recombinant activated protein C attenuated these responses in a dose-response manner. Interleukin-6 and MDA concentrations were increased by lower-dose therapy, but attenuated significantly by the higher-dose infusion at 5 mg/kg/h. Apoptosis was attenuated by both the lower and the higher dose, but more so with the higher dose. CONCLUSIONS: These data can assist in establishing an optimal dose and infusion time of this drug for extrapolation to therapy of human beings. The goal now is to elucidate these findings further so that the maximum benefit of the drug may be achieved with the least possible harmful effects.

An exploration of mammographers' attitudes towards the use of social media for providing breast screening information to clients.

INTRODUCTION: Increasingly patients and clients of health services are using social media to locate information about medical procedures and outcomes. There is increasing pressure for health professionals to engage in on-line spaces to provide clear and accurate information to their patient community. Research suggests there are some anxieties on the part of practitioners to do this. This study aimed to explore the attitudes of the NHS breast screening programme workforce towards engaging in online discussions with clients about breast screening. METHOD: 78 practitioners, representing a range of professional roles within the NHS Breast Screening Programme, attended one of 4 workshops. We used a Nominal Group Technique to identify and rank responses to the question: "What are the challenges that practitioners face in using SoME as part of their role?" Responses were categorised into themes. Participants were also asked to identify solutions to these challenges. RESULTS: Challenges: We identified two overarching themes: (1) Working within boundaries: which was further categorised into (a) Professional/legal accountability; (b) Information accuracy and (c)Time as a boundary, and (2) Support: further categorised into (a) Employer and (b) Manager. Solutions: These included: training in technical and interactional aspects of on-line communication and a responsibility to better understand employer and professional body SoMe policies. CONCLUSION: The study participants appeared willing and motivated to engage in SoMe. However, in keeping with the literature from other disciplines, a number of challenges need to be overcome for its use to be adopted more widely by breast screening professionals.

The effect of shock resuscitation fluids on apoptosis.

BACKGROUND: Recent data suggest that the type of resuscitation fluid used to treat hemorrhagic shock contributes to cellular dysfunction METHODS: Rats were hemorrhaged, exposed to a hypovolemic shock period for 75 minutes, and then resuscitated for 1 hour. Treatment animals were assigned randomly to lactate Ringer's solution, normal saline solution, bicarbonate Ringer's solution, hypertonic saline solution, rat plasma solution, ketone Ringer's solution, or nonresuscitation. After resuscitation, lung and liver samples were collected and evaluated for apoptosis by using ligation-mediated polymerase chain reaction. RESULTS: Nonresuscitated shock rats had significantly higher levels of apoptosis in lung and liver. Rats treated with normal saline solution, bicarbonate Ringer's solution, ketone Ringer's solution, and hypertonic saline solution had significantly lower levels of apoptosis in lung compared with nonresuscitated animals. Rats treated with bicarbonate Ringer's solution and ketone Ringer's solution had significantly lower levels of apoptosis in liver tissue when compared with nonresuscitated animals. CONCLUSIONS: Cellular damage results from hemorrhagic shock. The use of resuscitation fluids decreases apoptosis during shock.

Sepsis following burns, trauma, and intra-abdominal infections.

In the last ten years anaerobic organisms have emerged as the major infecting agent in surgical patients. While these groups of organisms including Bacteroides fragilis, clostridia, and anaerobic cocci persist, there has, in addition, developed in the last few years a virulent group of nosocomial infections, and modern management of sepsis is primarily directed at gram-negative and anaerobic infections, which include nosocomial infections, for example, those caused by the Serratia group. Much has been learned about control of infections from the patient who has sustained thermal injury. While topical water-soluble antibiotics have been a remarkable advance in the care of the burn patient, systemic and subeschar antibiotics have proved essential in the management of severe burn injury. There is increasing evidence that there is remarkable interference with host defense mechanisms in patients who have sustained burns or significant trauma or intraabdominal infection. The patient sustaining nonthermal traumatic injury also sustains reduction in host resistance. Because of this and the additional initial contamination, in the traumatized patient antibiotic therapy should be started early and as a therapeutic measure. Newer localization techniques, including sonography and computed axial tomography scanning, have helped localize abdominal infections early. Specific antimicrobial therapy may be begun as an adjunct to the surgical therapy of intra-abdominal infection.

Predicting postoperative pulmonary complications. Is it a real problem?

To identify predictors of postoperative pulmonary complications, a population of 278 patients, mainly hypertensive and diabetic patients undergoing elective general surgery was studied; 60% of the patients underwent abdominal surgery. Of the 278 patients, 6% had postoperative pulmonary complications: 3% had radiographic evidence of infiltrates or segmental atelectasis and 3% had clinical evidence of atelectasis. Among the two thirds of patients undergoing abdominal surgery, only patients with underlying asthma or chronic bronchitis were at increased risk. Generally, patients with better exercise tolerance by self-report, walking distance, or cardiovascular classification had lower rates. Pulmonary function tests did not help to delineate patients at higher risk of postoperative pulmonary complications. Simple clinical information provided as much data about the patients' risk as pulmonary function tests. Many of these complications occurred in patients who sustained other types of postoperative morbidity, suggesting that predicting and preventing postoperative cardiac morbidity may be the best approach to reducing postoperative pulmonary morbidity.

The post-operative electrocardiogram and creatine kinase: implications for diagnosis of myocardial infarction after non-cardiac surgery.

The objective of this study was to evaluate different approaches to the diagnosis of post-operative myocardial infarction. A total of 232 patients, mostly hypertensive and/or diabetic patients, who were undergoing elective non-cardiac surgery were evaluated pre-operatively. They were followed serially from the day of operation to discharge or the sixth post-operative day with daily clinical evaluations, electrocardiograms, creatine kinase and creatine kinase isoenzymes. In total 22% (51/232) of the patients had post-operative ECG changes in two or more leads. Only 1% developed new Q waves; most of the changes involved changes in the T or ST segments. Seventy percent of patients who had changes in their electrocardiogram were completely asymptomatic. The highest risk of ECG changes or symptoms occurred on the day of operation and the first post-operative day; evidence of post-operative infarction was infrequent after the second post-operative day. Creatine kinase levels rose an average of 250-300 IU on the first and second post-operative day (also the peak time for post-operative ECG changes), reducing its utility as an adjunct to the diagnosis of post-operative infarctions. Importantly, 52% (12/23) of the patients who had greater than or equal to 5% MB isoenzyme had neither ECG changes nor symptoms; the diagnosis of a myocardial infarction should not be made in these patients. In summary, most patients who experience ischemia or infarction post-operatively are asymptomatic. Symptoms should not be required for the diagnosis of post-operative infarction. Seemingly minor differences in criteria can produce major discrepancies in post-operative myocardial infarction rates (from 1 to 9%). The development of a final set of criteria will require further study but the diagnosis of post-operative infarction should probably be based on ECG changes, their duration and consistency, and the association of a positive MB fraction.

The effect of increasing end-expiratory pressure on extravascular lung water.

The objective of this study was to define the response of extravascular lung water (EVLW) to different levels of positive end-expiratory pressure (PEEP) following a standardized oleic acid injury to the lung. All animals responded to the injection of intravenous oleic acid by the rapid development of hypoxemia. There was a twofold increase in EVLW during the first 3 hours after oleic acid injection which remained stable during the remainder of the experiment, including periods on PEEP. Intrapulmonary shunt (Qs/Qt) increased significantly (P less than 0.001) during the first hour following oleic acid injection. PEEP therapy resulted in an immediate decrease in Qs/Qt and amelioration of the hypoxemia. Return to zero PEEP resulted in a rapid decrease in PaO2 with concomitant increase in Qs/Qt by the end of the experiment. The oxygen transport in the animals did not improve significantly with the addition of PEEP. This was due to the decrease in cardiac output that more than offset the effects of a diminished Qs/Qt with PEEP. This study indicates that the mechanism by which PEEP improves oxygenation does not appear to be mediated by effect on lung water. The study also emphasizes the importance of determining oxygen transport when managing patients on PEEP.

Measurement of lung water in inhalation injury.

Pulmonary inhalation injury is a major cause of morbidity and mortality rates in burn victims. But the pathophysiology of parenchymal inhalation injury has not been fully elucidated. In this study, extravascular lung water volume (EVLW) was measured in burn patients with and without inhalation injury. Patients with parenchymal inhalation injury (group II) had elevated admission extravascular lung water volumes (10.12 +/- 3.43 ml/kg), whereas patients without parenchymal injury (group I) had significantly lower lung water values (3.91 +/- 1.49 ml/kg). Both accumulation of EVLW and ventilation-perfusion abnormalities in the group II patients occurred within hours of smoke inhalation. But the severity of inhalation injury did not consistently correlate with the elevation of EVLW. This indicated that both interstitial edema and ventilation-perfusion imbalance contributed, in varying degrees, to the pathophysiology of inhalation injury. In this study, the general clinical criteria for inhalation injury--presence of facial or oropharyngeal burns, carboxyhemoglobin levels, carbonaceous sputum, or closed space injury--did not differentiate patients with airway injury only from those with parenchymal injury. Patients in both groups who died of sepsis had significant (P less than 0.01) increases in EVLW 24 to 48 hours after the clinical onset of sepsis. The normal hydrostatic pressures in these septic patients suggested that the increase in EVLW observed with sepsis was due to an increase in pulmonary capillary membrane permeability.

The effect of septic shock on skeletal muscle action potentials in the primate.

Techniques developed for the in vivo study of cellular physiology have been applied to septic shock in primates. Measurements of skeletal muscle transmembrane resting and action potentials were correlated with an analysis of fluid and electrolyte changes in the intracellular and extracellular compartments of skeletal muscle. The data obtained indicated a marked depletion of muscle extracellular water and an increase in intracellular sodium chloride and water content during shock. The significant decrease of resting membrane potential was associated with a decrease in amplitude of the action potential and prolongation of both the repolarization and depolarization time. In addition, there was a decrease of muscle intracellular potassium concentration during shock. This study demonstrates that the alterations in cellular membranes in hemorrhagic shock and septic shock are similar.

Extracorporeal life support for the treatment of adult respiratory distress syndrome after burn injury.

The pediatric population comprises 38% of hospital admissions for burns in the United States. In the age group of 1- to 14-year-olds, a 62% total body surface area burn represents the median lethal dose and carries a lower mortality rate for burn size than in infants or adults. Adult respiratory distress syndrome (ARDS) is a common accompaniment to severe burn injury. Mortality rates of 50% to 80% are expected once ARDS occurs. This is a report of an 11-month-old boy who had fulminant ARDS after a 32% total body surface area second degree burn. After conventional therapy with maximum mechanical ventilatory support failed, salvage therapy with extracorporeal membrane oxygenation (ECMO) was instituted. ECMO was successfully terminated after 28 days. Open lung biopsy specimens obtained before instituting ECMO and on ECMO day 26 exhibited severe but histologically reversible lung disease and improved alveolar aeration as a result of treatment. This is the first reported survival of a pediatric patient with thermal injury and ARDS by using ECMO for the treatment of respiratory failure.

Additive effects of thermal injury and infection on the small bowel.

Thermal injury is associated with functional alterations of multiple organ systems, including the gastrointestinal tract. To study the effects of ongoing infection after thermal injury on bowel mass, composition, and blood flow, male Wistar rats were randomized to receive either 30% scald burn, 30% scald burn with Pseudomonas aeruginosa wound inoculation, sham burn, or sham burn with pair feeding to burned and infected animals. On days 3 and 7 after injury, intestinal blood flow was measured with 51Cr-labeled microspheres, and intestinal mass and composition were analyzed. Burned and infected animals demonstrated a chronic loss of small bowel mass not seen in burned animals without infection by day 7 after injury. Compositional alterations of the small bowels of burned and infected animals included protein wasting similar to but occurring earlier than that seen with anorexia alone and significantly decreased deoxyribonucleic acid and ribonucleic acid content, whereas tissue water content remained unchanged. These chronic intestinal alterations in the burned and infected group could not be explained by ongoing ischemia because intestinal blood flow in these animals was not significantly altered at either time point, implying mediation by other pathophysiologic mechanisms.

Alterations of pulmonary gas exchange after superimposed carbon monoxide poisoning in acute lung injury.

BACKGROUND: Smoke inhalation injury produces substantial morbidity and mortality caused both by immediate catastrophic pulmonary failure and by the subsequent development of pneumonia. Although carbon monoxide (CO) poisoning is present to a degree in nearly all instances of smoke inhalation, the importance of CO in the pathogenesis of smoke inhalation injury remains controversial because smoke contains numerous other potential pulmonary toxins such as aldehydes, chlorine gas, and hydrochloric acid. This study was performed to determine whether CO poisoning acts as a cofactor in the evolution of inhalation injury. METHODS: Four groups of anesthetized dogs received ventilation with 1% CO in room air alone, intratracheal instillation of 2.0 ml/kg 0.1 N hydrochloric acid (HCl) alone, or acid either immediately or 30 minutes before CO. Ventilation/perfusion relationships were measured for 4 hours thereafter with the multiple inert gas elimination technique. RESULTS: Acid instillation established 30 minutes before CO poisoning resulted in significantly decreased carboxyhemoglobin concentrations after ventilation with 1% CO in air for 10 minutes. However, CO elimination was markedly delayed in both acid-challenged groups ventilated with CO. Moreover, acid instillation immediately before CO poisoning significantly exacerbated the development of ventilation/perfusion inequality caused by the acid, because the development of shunt was accelerated. CONCLUSIONS: CO poisoning is an important cofactor in the development of inhalation injury by acceleration of the development of ventilation/perfusion inequality after inhalation.

Permeability of red-cell membrane to adenosine triphosphate (ATP) molecules during hemorrhagic shock.

The findings of decreased adenosine triphosphate (ATP) levels in liver, kidney, and other tissues of animals in hemorrhagic shock were the rationale for previous experimental attempts to improve cell function by administration of fluids that contained high concentrations of ATP. The beneficial effects of this resuscitation, which are still controversial, were attributed to cellular uptake of ATP--it was assumed that cell membranes are permeable to this substrate. The effect of a high concentration of ATP in extracellular medium on intracellular ATP content was studied by using red blood cells (RBCs) from rabbits in control (normal) and in hemorrhagic shock states. The glucose-depleted RBCs were incubated in medium with 5 mMol/L ATP, and their ATP concentration fell markedly to the same level as seen in glucose-depleted RBCs incubated without ATP. The decrease of ATP in glucose-repleted RBCs, incubated with or without ATP, also did not show any significant difference. Similar to parallel experiments that used normal RBCs, the high extracellular ATP content did not substantially affect the intracellular ATP concentration in RBCs from animals in shock. This study indicates that ATP molecules in extracellular medium cannot penetrate either the normal RBC membrane or the RBC membrane during shock.

Effects of isotonic saline solution resuscitation on blood coagulation in uncontrolled hemorrhage.

BACKGROUND: It has been suggested that fluid resuscitation before surgical control of hemorrhage may lead to increased bleeding because of the elevated blood pressures and clotting factor dilution. This study was designed to assess the effects of isotonic saline solution resuscitation on blood coagulation during uncontrolled hemorrhage. METHODS: Twenty-four female Sprague-Dawley rats were randomized into four groups with different resuscitation regimens: group A, no resuscitation; group B, 40 ml/kg in 4 minutes; group C, 80 ml/kg in 4 minutes; and group D, 80 ml/kg in 1 minute. Baseline blood samples were collected just before a sharp resection of 75% of the tail to initiate the hemorrhage; 15 minutes later the resuscitation began. Additional blood samples were obtained at 60 minutes after resection. The blood was analyzed for platelets, fibrinogen, prothrombin time, and activated partial thromboplastin time. RESULTS: The largest differences between time 0 and 60 minutes were observed in group D with platelets decreasing 43.36% +/- 7.86%, fibrinogen decreasing 57.10% +/- 16.88%, and prothrombin time increasing from an average 16.5 to 19.2 seconds. These differences was statistiacally significant (p <0.05) with the Student's test. CONCLUSIONS: The results suggested that even though the volume of resuscitation fluid did not appear to affect clotting time when compared with that of nonresuscitated animals, the rate of extremely large volume infusions may play an important role in the cessation of bleeding and consequently in the management of uncontrolled hemorrhagic shock.

Early isotonic saline resuscitation from uncontrolled hemorrhage in rats.

BACKGROUND: Attempts to modify traditional fluid resuscitation have been based on animal models that evaluate several variables including anesthesia. This study presents the effects of early saline resuscitation from severe uncontrolled hemorrhage unanesthetized rats. METHODS: Sixty-three female Sprague-Dawley rats were equally divided into three groups: group A, nonresuscitated; and groups B and C, resuscitated ;with isotonic saline (40 and 80 mL/kg, respectively). Hemodynamics, blood loss, survival time, and mortality were recorded for 360 minutes after the hemorrhage, which was initiated by 75% resection of the tail. RESULTS: In group C, 80 mL/kg of saline significantly lowered mortality (24% vs 76% and 71% for groups A and B, respectively) with concomitant increases in mean survival time (241 +/- 103 min vs 146 +/- 108 and 175 +/- 92 min for groups A and B, respectively). There were no statistically significant differences in blood loss, hematocrit, or hemodynamic parameters among the groups. CONCLUSIONS: Early and adequate isotonic saline resuscitation of unanesthetized rats improved outcome despite continuing hemorrhage. The significantly lower mortality rate and increased survival time were not a result of transiently improved arterial pressure and did not correlate with blood loss. No significant bleeding increases were noted in the resuscitated groups.

Influence of hypercortisolemia on soluble tumor necrosis factor receptor II and interleukin-1 receptor antagonist responses to endotoxin in human beings.

BACKGROUND: We have previously reported that the antecedent administration of glucocorticoids altered both the hormonal and proinflammatory cytokine responses to lipopolysaccharide (LPS) when administered to human volunteers. In that study, subjects with vastly exaggerated levels of tumor necrosis factor (TNF) and interleukin (IL)-6 12 and 144 hours after cortisol infusion exhibited hemodynamic and hormonal responses no different from those of untreated subjects after endotoxin. The current study examined levels of the antiinflammatory cytokines interleukin-1 receptor antagonist (IL-1ra) and soluble receptors to tumor necrosis factor (sTNF-R) in the same setting of the previous report. METHODS: Hydrocortisone succinate was infused into healthy volunteers. LPS was then injected immediately or was delayed by 6, 12, or 144 hours (C, C-6, C-12, and C-144, respectively). Subjects receiving LPS alone served as controls. Plasma was analyzed to determine levels of TNF, sTNF-R and IL-1ra by enzyme-linked immunosorbent assay before administration of LPS and at 30-minute intervals after administration of LPS for 6 hours. RESULTS: Levels of sTNF-R increased after LPS administration in all groups (p < 0.05 versus baseline) with a significantly higher level recorded in the subjects having received hydrocortisone 144 hours before (C-144, p < 0.05 versus all other groups). TNF levels remained undetectable in association with immediate infusion of LPS (C) and the relatively short delay group (C6). This cytokine peaked 90 minutes after LPS in all other groups, with a significantly higher peak in the C-144 subjects when compared with controls. IL-1ra levels rose in all groups but to a lesser extent in the C group (p < 0.05). CONCLUSIONS: These data confirm that glucocorticoids influence the production of both sTNF-R and IL-1ra. The potential for an exaggerated response of sTNF-R exists for an extended period of time after exposure to glucocorticoids.

Effect of hypothermia on cellular membrane function during low-flow extracorporeal circulation.

The use of systemic hypothermia is known to allow recovery from potentially lethal states of profound hypoperfusion or total circulatory arrest. While the cellular alterations accompanying states of decreased perfusion in skeletal muscle are well defined, little is known regarding the impact of coexistent hypothermia. To investigate this issue, nine dogs were placed on total cardiopulmonary bypass (CPB) and perfused in nonpulsatile fashion. The following flow and temperature parameters were used in three different perfusion models: 3.5 L/min/m2 at 23 degrees C (group A, n = 3), 1.6 L/min/m2 at 37 degrees C (group B, n = 3), and 1.6 L/min/m2 at 23 degrees C (group C, n = 3). Assessment of cellular function in a hind limb adductor muscle by measurement of resting transmembrane potential difference (Em) and determination of tissue electrolyte distribution in a biopsy specimen was performed in the control state and again after 60 minutes of total CPB. Low-flow/hypothermic CPB (group C) was associated with depolarization of resting Em to -63.3 +/- 3.2 mV from a control value of -87.0 +/- 1.3 mV (p less than 0.05), an increase in the calculated intracellular Na ([Na]i) to 16.4 +/- 4.0 mEq/L from a control value of 7.6 +/- 1.4 mEq/L (p less than 0.05), and an increase in the ratio of the selective membrane permeabilities of Na+ to K+ (pNa/pK), to 0.067 +/- 0.013 from a control value of 0.013 +/- 0.002 (p less than 0.05). In contrast, resting Em was maintained at -86.4 +/- 6.1 mv during normal-flow/hypothermic CPB (group A), while low-flow/normothermic CPB (group B) produced an intermediate depolarization to -75.2 +/- 3.0 mV (p less than 0.05). Neither [Na]i or pNa/pK was altered significantly in group A or group B dogs. These data characterize a physiologic alteration in the cellular membrane function of skeletal muscle during low-flow/hypothermic CPB, which is similar in many respects to that accompanying hemorrhagic shock. This suggests that during periods of profound hypothermia certain flow-related derangements in skeletal muscle are not obviated and may be exacerbated.