Sucralfate suspension versus titrated antacid for the prevention of acute stress-related gastrointestinal hemorrhage in critically ill patients.

Seventy-four medical and surgical patients having a minimum of two risk factors for stress-related gastric mucosal bleeding were prospectively selected randomly to receive prophylaxis by antacid titration (to maintain a gastric pH of more than 4) or with sucralfate suspension (1 g/10 ml every four hours). Gastric aspirates were monitored every two hours for pH and overt and occult bleeding. Despite a significantly greater severity of illness in the sucralfate group (p less than 0.01), no significant difference in overt or occult bleeding between the groups could be demonstrated. Low-grade occult blood loss occurred frequently in both groups, but only one of the 74 patients (four risk factors, sucralfate group) had significant stress-related bleeding as defined by preset criteria and documented by endoscopy. The effectiveness of sucralfate appeared unrelated to acid neutralization in keeping with its classification as a cytoprotective agent. There were eight antacid-related side effects (four severe diarrhea, four hypermagnesemia), and none related to sucralfate. Sucralfate suspension was safe and effective and had fewer side effects than antacid titration for the prophylaxis of stress-related bleeding in critically ill patients.

Cultured mouse keratinocyte allografts prime for accelerated second set rejection and enhanced cytotoxic lymphocyte response.

It has been reported that cultured keratinocyte (CK) allografts are not rejected in mice, unlike in other species. Several reports have suggested that mouse CK allografts are incapable of stimulating a primary alloresponse, including sensitization of recipients to alloantigens. In this study, we investigated the immunogenicity of mouse CK allografts in vivo by determining whether CK allografts primed for a second set rejection response. First, we grafted mice with either CK allografts, CK autografts, full-thickness (FT) allografts, or no graft at all. We then regrafted mice 4 weeks later with a tail skin allograft. Mice grafted with CK allografts rejected second allografts as rapidly and as vigorously as mice grafted with FT flank allografts. Next, we tested whether CK allograft primed recipients for enhanced CTL responses. We found that mice grafted with CK allografts generated a significantly enhanced CTL alloreactive response after in vitro stimulation. The response was similar to that of mice grafted with FT skin allografts. With evidence that CK allografts primed, we biopsied wounds immediately after CK allografting and, using Western immunoblotting, found that CK allografts had substantial expression of MHC class II antigens in vivo. We conclude from the results of our studies that mouse CK allografts unequivocally prime recipients to alloantigens in vivo and suggest that a possible mechanism for alloantigen priming may be CK allograft expression of MHC class II antigens.

Burn injury impairs second-set rejection and CTL reactivity in mice primed by cultured keratinocyte allografts.

Cultured keratinocyte (CK) allografts have limited antigenicity and have been used as a skin replacement in patients with massive thermal injury. Recent data indicate that CK grafts are more immunogenic than previously believed and could compromise wound healing in the immunocompetent host. The purpose of this study was to determine if the immunosuppression of burn injury might affect the alloantigen response and minimize sensitization to CK allografts. CBA mice received a 0%, 20%, or 40% burn that was partially excised three days later and grafted with a full-thickness (FT) skin allograft, CK allograft, or CK autograft. Two weeks postburn, mice received FT tail skin allografts, which were observed for rejection. We observed that FT and CK allografts primed the unburned host with equal efficacy. However, burn injury selectively minimized priming by CK allografts, resulting in delayed rejection of second-set allografts. With evidence that burn injury inhibits host sensitization to CK allografts, we then examined the effect of burn size on CTL alloreactivity. Additional CBA mice underwent burn injury, excision, and grafting as described above. Host splenocytes were harvested two weeks later and tested on radiolabeled targets for allospecific cytotoxicity. CTLs from unburned mice primed with FT allografts demonstrated the greatest CTL lysis, followed next by CTLs from unburned mice covered with CK allografts. Burn injury inhibited CTL activity as a function of wound size. Activity of CTLs from burned mice primed with CK allografts improved after in vitro allostimulation but remained below that of CTLs from unburned, unprimed mice. We conclude that burn injury selectively inhibits the allospecific response to CK allografts. The decreased immunogenicity of CK allografts, when used for burn wound coverage, may improve the long-term survival of allogeneic keratinocytes, enhancing their potential as a biologic skin replacement.

The impact of femur fracture with associated soft tissue injury on immune function and intestinal permeability.

Alterations in intestinal permeability and immune function were investigated in a murine femur fracture (FFx) model. We postulated that soft tissue injury associated with closed FFx (crush injury) would result in greater immunosuppression that open FFx (surgical division). AKR mice were randomized to four groups (Normal, Sham, Open FFx, Closed FFx) and studied at 24 and 96 h post-injury. Immune function was assessed by splenocyte blastogenic response and class-specific immunoglobulin production. Intestinal permeability was assessed by measurement of whole blood fluorometry after gavage administration of fluorescein-dextran (FITC-dextran). Closed FFx is associated with increased splenocyte blastogenesis and increased immunoglobulin production at 24 h post-injury. This immunostimulatory response was associated with altered intestinal permeability early after injury (FITC-dextran:.185 +/- .070 Closed FFx vs. .069 +/- .011 Normal, p = .06). Immunosuppression was evident at 96 h post-injury in the closed FFx group, documented by significant reductions in splenocyte blastogenesis to all mitogens studied. The Open FFx group did not demonstrate any reduction in splenocyte blastogenesis at 96 h post-injury. These data suggest that the soft tissue injury associated with Closed FFx is associated with significant immunosuppression and altered gastrointestinal permeability, which may adversely affect the host by increasing the relative risk of post-trauma infection.

Critical care education in general surgery residencies.

Surgical critical care (SCC) was recently identified as an essential component of general surgery by the American Board of Surgery (ABS). Previous studies have found limited attention to critical care education in general surgery programs. This survey was developed to determine the changes in critical care education, following the emphasis by the ABS. The survey determined the format for SCC education, the time and resources committed, and the views of the program directors toward SCC. Program directors of all 296 approved general surgery residencies were surveyed, with a 79% response. Most program directors (91%) agree that SCC is an essential component of general surgery, and 72% believe a separate intensive care unit (ICU) rotation should be used in SCC education. Education in SCC was provided by a separate ICU service in 110 (47%) of the programs. The remaining 53% used care of patients in the ICU during traditional services as their educational experience. The average ICU rotation for surgery residents was 9 weeks and usually occurred in the second year of training. In 97% of the 110 programs with an ICU service, lectures and conferences were conducted regularly. Seventeen programs sponsored critical care fellowships, and 25 additional programs were considering them. Ninety percent of surgical ICU services had faculty that consisted exclusively of surgeons or surgeons and other specialists. Only 53% of surgeons attending on an ICU service had a reduction in their other responsibilities. Despite overwhelming agreement that critical care is an essential component of general surgery, less than half of the training programs have an ICU service to coordinate resident education in SCC. If surgeons are to continue to provide total care to their patients, there needs to be increased commitment to SCC education.

Cultured keratinocyte allografts fail to induce sensitization in vivo.

BACKGROUND: The use of cultured keratinocyte (CK) allografts for burn wounds offers a potentially unlimited supply of skin. It is unknown, however, whether CK allografts induce rejection in vivo. This study investigated the induction of immune responsiveness to CK allografts as measured by mixed lymphocyte response and serum cytotoxic antibody. METHODS: Female CBA mice (n = 160) were randomized to four equal groups, each receiving a 3 cm2 flank graft of autologous CBA CK (Auto CK), allogeneic C57BL/6 CK (Allo CK), C57BL/6 full thickness skin (Allo FT), or Sham. Graft take was assessed by gross and histologic examinations. Unidirectional mixed lymphocyte response was measured with graft recipient and donor splenocytes by use of tritiated thymidine uptake. Stimulation indexes were calculated. Serum cytotoxic antibody was measured by coculturing graft recipient serum with donor splenocytes and rabbit complement and assessing resultant cell killing. RESULTS: Overall graft take was 50% for Allo CK and 74% for Auto CK, Allo FT, but not Allo CK, were associated with significantly increased stimulation indexes compared with Auto CK and Sham (p < 0.01). Allo FT, but not Allo CK, resulted in elevated titers of alloantibody, reaching significant levels 10 days after grafting (p < 0.05). CONCLUSIONS: CK allografts do not result in increased in vitro T cell responses or enhanced alloantibody formation, indicating that sensitization to major histocompatibility antigens by CK does not occur. These data suggest that CK allografts may provide a possible source of grafts for victims of large burn wounds.

Early, complete burn wound excision partially restores cytotoxic T lymphocyte function.

BACKGROUND: Cytotoxic lymphocytes (CTLs) are an important component of immune function, involved in antigen recognition and resistance to viral infection. Burn injury suppresses cell-mediated immunity, induces allograft tolerance, and increases the risk of viral infection, but the mechanisms are not well understood. This study analyzes the effect of burn size and burn wound excision on CTL activity. METHODS: Anesthetized CBA mice (n = 12) received a 0%, 20%, or 40% body surface area contact burn. Additional mice (n = 16) received a 40% burn that was totally, partially, or not excised 72 hours after burn. Excised areas were covered with normal, syngeneic skin. Two weeks later harvested splenocytes were cocultured with allogeneic stimulators. CTL activity was determined by a 51Cr release assay, in which CTL effectors were tested on allogeneic, radiolabeled targets. Dilution curves of CTL activity were compared by ANOVA: RESULTS: Both 20% and 40% burns significantly inhibited CTL activity (p < 0.05). Total but not partial excision of a 40% burn restored CTL activity (p < 0.01). Both total and partial wound excision also improved survival (p < 0.05). CONCLUSIONS: Burn injury inhibits CTL activity in a size-dependent manner, and total wound excision significantly improves both CTL function and survival after injury. This study suggests a mechanism for the immunosuppressive effects of burn injury and provides an immunologic rationale for early, complete burn wound excision.

Accuracy of administrative data in trauma.

BACKGROUND: Accurate data are needed to evaluate outcomes, therapeutics, and quality of care. This study assesses the accuracy of administrative databases in recording information about trauma patients. METHODS: Patients with thoracic aorta injury were identified with a state trauma registry, and the medical records were reviewed. Data collected were compared to administrative data on patients with thoracic aorta injuries, at the same hospitals in the same time period. RESULTS: Fifteen patients (16.3%) with thoracic aorta injury were not recorded in the administrative database, and 23 patients (18.7%) were misdiagnosed. Ninety-one patients were found in both data sources. The administrative database significantly (P < .05) underrecorded abdominal injuries (50 vs 35), orthopedic injuries (117 vs 75), and chest injuries (77 vs 48). The number of aortograms (78 vs 8), type of operative procedures (use of graft; 70 vs 30), use of bypass (35 vs 16), and complications (77 vs 33) were underreported (P < .05). The Injury Severity Score was underestimated by the administrative database (38.65 +/- 12.41 vs 25.66 +/- 9.53; P < .05). CONCLUSIONS: Administrative data lack accuracy in the recording of associated injury, injury severity, diagnostic, and procedural data. Whether these data should be used to evaluate treatment or quality of care in trauma is questionable.

CD8(+) T cells express a T-helper 1--like phenotype after burn injury.

BACKGROUND: Previous studies suggest that CD8(+) T cells are immunosuppressive after burn injury, but recent reports indicate that CD8(+) T cells have several functions similar to CD4(+) T cells, including the secretion of cytokines. This study uses HY male antigen in transgenic HY female mice to determine the antigen-specific response of activated CD8(+) T cells after burn injury. METHODS: HY TCR transgenic female mice underwent burn or sham injury. Seventy-two hours after the burn, splenocytes were stimulated with 20 micromol/L HY peptide for 16, 48, and 64 hours; cellular proliferation, intracellular interferon-gamma and interleukin-2, and apoptosis were measured. RESULTS: Burn injury significantly impaired proliferation to HY antigen (P < or =.05). Activated CD8(+) T cells from burned mice showed increased intracellular interferon-gamma and interleukin-2 16 hours after stimulation compared with sham (P < or =.05) and at no time was less than control mice. The percent of CD8(+) T cells decreased with the time of stimulation but was not due to apoptosis by Annexin V staining. CONCLUSIONS: Activated CD8(+) T cells express a T(h1)-like phenotype after burn injury. This provides evidence that CD8(+) T cells are not simply suppressive and that is consistent with data that CD4(+) T cells are primed for a T(h1) response after burn injury.

Skin replacements. The biotechnological quest for optimal wound closure.

Extensive skin loss from a variety of conditions is associated with significant functional morbidity and loss of life. In many patients, a limited number of donor sites available for harvesting autologous split-thickness skin grafts prevents early, effective, and permanent wound closure. In the past 25 years, significant biotechnological advancements have been made in defining the criteria and manufacturing ingredients in materials that could serve as skin replacements for permanent wound closure. The optimal skin replacement should have the functional and cosmetic properties of the dermis and the epidermis. It should provide rapid, functional wound coverage and barrier protection to microorganisms, normalize fluid flux and hypermetabolism, and provide long-term stability without contraction or hypertrophic scarring. In addition, the optimal skin replacement should be nontoxic, easily stored and used, and relatively cost-effective. This report will discuss the two major skin replacement designs available today, cultured keratinocyte grafts and bioartificial bilaminate systems, outline the advantages and disadvantages of each material, report the results of clinical trials for each, and speculate on the potential for each material to serve as a practical skin replacement.

Effect of dietary fish oil on plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha levels in septic rats.

Increased mortality from sepsis is associated with high levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha). Linoleic acid, an n-6 essential fatty acid, is the usual precursor of TXB2 and PGF1 alpha, while fish oil is rich in n-3 essential fatty acid, the precursor of less active moieties. Rats were fed chow, an essential fatty acid-deficient diet, or an essential fatty acid-deficient diet supplemented with linoleic acid or fish oil for 2 weeks. The animals then underwent a sham operation or cecal ligation and puncture to induce sepsis. Six hours later, blood was obtained for analysis. The chow and linoleic acid diets produced significant (twofold to fivefold) increases in levels of both TXB2 and PGF1 alpha after sepsis. The essential fatty acid-deficient diet and fish oil diet protected against increases in levels of TXB2 or PGF1 alpha during sepsis. Dietary restriction of linoleic acid or fish oil supplementation may play an important role in altering the inflammatory mediator response to sepsis.

Selective nonoperative management of blunt liver injury using computed tomography.

Computed tomographic (CT) scans are used to evaluate victims of blunt trauma for abdominal injury when reasons for immediate laparotomy are not present. Twenty-four patients whose CT scans showed liver injuries that were small parenchymal lacerations or intrahepatic hematomas were managed without laparotomy. Intra-abdominal blood was absent or estimated to be less than 250 mL in volume. None of the patients were in shock; six patients required transfusions, none for acute abdominal bleeding. None of these patients subsequently required laparotomy or showed hepatobiliary problems at a follow-up examination less than one year later. Five follow-up scans showed varying degrees of resolution. Two patients died of severe head injury, but the liver injury did not contribute to the cause of death. Other patients with more severe blunt liver injury who were treated nonoperatively developed significant complications that required delayed surgery. It seems that patients with limited liver injury diagnosed by CT scan and selected by strictly applied criteria can be managed safely without laparotomy in a setting where rapid evaluation and treatment of any potential complication is available.

The impact of laparoscopic cholecystectomy on the management and outcome of biliary tract disease in North Carolina: a statewide, population-based, time-series analysis.

BACKGROUND: Laparoscopic cholecystectomy (LC) has had a major impact on the treatment of patients with biliary tract disease, but the magnitude and the details of its effects on biliary surgery remain incompletely described. The purpose of this study was to perform a statewide, population-based, time-series analysis of the effects of LC on biliary surgery. STUDY DESIGN: Patient data were obtained from the statewide hospital discharge database that collects data from all 157 hospitals in the state of North Carolina. All patients with hospital admissions for biliary tract disease from 1988 through 1993 were selected for analysis. RESULTS: The use of open cholecystectomy (OC) dropped from 100 percent of all cholecystectomies in 1988 to 32.3 percent in 1993, while LC increased from eight cases in 1988 to over 7,800 per year in 1993. The increase in the rate of LC was not associated with an increase in the overall rate of cholecystectomy. Bile duct (BD) repairs increased from 13 in 1988 to a high of 36 in 1992. There was a strong, statistically significant correlation between the rate of LCs and the rate of BD repairs (R = 0.89, p = 0.0001). Hospital charges and component charges were lower for patients having elective LC compared to those having elective OC (p = 0.001). This remained true after stratification by age and type of gallbladder disease. Hospital stays were shorter for patients having LC than for those having OC (p = 0.001 for all). Surgeons in smaller hospitals were slower at adopting LC. Younger and board certified surgeons adopted LC more rapidly than older and non-board certified surgeons. CONCLUSIONS: In North Carolina, LCs progressed from nonexistent to the dominant approach for managing patients with cholelithiasis in a matter of a few years. Associated with this change were shorter hospitalizations and lower charges. Contrary to other published reports, North Carolina did not experience an increase in the overall rate of cholecystectomy with the adoption of LC. There was a highly correlated increase in the rate of bile duct repairs in the first years of the study.

Prospective analysis of outcome after cardiopulmonary resuscitation in critically ill surgical patients.

BACKGROUND: This study was done to examine the outcome of cardiopulmonary resuscitation (CPR) in the surgical intensive care unit (SICU) and to identify factors preceding cardiopulmonary arrest that could predict survival. STUDY DESIGN: We prospectively collected demographic, laboratory, diagnostic, and complications data in our SICU database on 5,237 consecutive patients and reviewed the charts of all patients receiving CPR. RESULTS: Cardiopulmonary resuscitation was performed upon 1.1 percent (55 of 5,237 patients) of patients in the SICU. Twenty-nine percent (16 of 55 patients) survived greater than 24 hours but died in the hospital, and 13 percent (seven of 55 patients) survived to discharge. No patient with a worsening Glasgow Coma Scale (GCS) score, acute physiology score (APS), or any acute organ failure who had cardiopulmonary arrest survived. Survival after CPR for patients with a stable or improving APS was 32 percent (p < 0.01). CONCLUSIONS: Patients in the SICU who survived CPR had a stable or improving clinical course as determined by APS and GCS score, and had not had acute organ failure. Patients who were critically ill with a declining clinical course did not survive after CPR.

Mortality from ruptured abdominal aortic aneurysms. A comparison of two series.

Series of ruptured abdominal aortic aneurysms from a municipal teaching hospital and from a group of private surgeons practicing at four community hospitals were compared for hemodynamic status and time to operation, as well as mortality. The overall mortality rate was 61 percent for the municipal hospital series and 32 percent for the community hospital series, which was significantly different (p = 0.003). The municipal hospital series had a significantly greater number of patients in shock before operation, as well as a greater number of patients transported directly to the operating room. The community hospital series had a significantly greater number of patients with a more than 6 hour delay in diagnosis and delays in surgical exploration. When those patients in shock who were brought directly to the operating room were compared, there was no statistical difference between the two series. Further reviews of ruptured abdominal aortic aneurysms should attempt to identify groups of patients by their hemodynamic status when evaluating treatment.

Pancreatic abscess: impact of computerized tomography on early diagnosis and surgery.

Pancreatic abscess continues to be a lethal complication of acute pancreatitis, with mortality rates of 40 percent in recent surgical series. A major factor contributing to this high mortality has been delay in diagnosis. When combined with diagnostic needle aspiration, computerized tomographic scanning has greatly enhanced the early detection of pancreatic abscesses. In a 4 year period at our institutions, 21 patients with proved pancreatic abscesses were evaluated early in their clinical course by computerized tomography. On follow-up ranging from 7 months to 3 1/2 years, there were only four deaths for a mortality rate of 19 percent. Many of the surviving patients had a long and protracted clinical course (mean length of hospitalization was 56 days) and reoperation for recurrent abscess or gastrointestinal complications was required in eight patients (38 percent). Computerized tomography proved to be of considerable value in localizing the site of de novo or recurrent pancreatic abscess and in detecting postoperative complications. An aggressive approach encompassing early computerized tomographic scanning with diagnostic needle aspiration appears to be a factor in the improved survival rate of these patients.

Necrotizing soft-tissue infections.

In the realm of clinical practice, this disease entity defies applicability to any classification scheme. Of paramount importance is the early identification of all necrotizing soft-tissue infections. This requires a high index of suspicion, aided by recognition of various risk factors and organ system dysfunction out of proportion to the extent of local signs and symptoms. Expedient, aggressive surgical therapy is imperative: resuscitation, wide débridement, and antibiotic therapy. Once the infection has been controlled, continued supportive care, reconstruction, and rehabilitation can proceed.

Abdominal trauma.

Abdominal trauma continues to be the major cause of morbidity and mortality in this country. Unnecessary deaths and complications can be minimized by improved resuscitation, evaluation, and treatment. Rapid resuscitation is necessary to save the unstable but salvageable patient with abdominal trauma. Accurate diagnosis and avoidance of unneeded surgery is an important goal of evaluation. However, most avoidable deaths result from failure to resuscitate and operate on surgically correctable injuries. When the diagnosis is in doubt and clinical judgment suggests surgery, exploration provides definitive treatment as well as diagnosis; moreover, the risks of negative exploration have become acceptable. The new techniques and diagnostic tools available are important in the management of abdominal trauma. These improved methods, however, still depend on experience and clinical judgment for application and determination of the best care for the injured patient.

Prevention of blood exposure. Body and facial protection.

Regardless of the specific clinical setting in the operating room, it is clear that better protection of all personnel is an appropriate objective in the current environment. Better protection through improved PPE and modification of operational practices is essential. A prompt response to blood contact when it does occur is likewise appropriate. With conscientious applications of methods to reduce blood exposure, it is hoped that the operating room can become a safer place with respect to occupational infections from bloodborne pathogens.

Critical care as an integral part of trauma care.

There appears to be reasonable evidence to support the concept of trauma centers, as well as ICUs for the critical care management of the seriously injured trauma patient. For optimal care of such patients, there must be effective delivery of such critical care. Despite some concerns as to who should provide such care to trauma patients, as well as all other patients, there is little debate over the goal of such treatment--that is, optimal care of these seriously injured patients. With this goal in mind, each institution must design a system that provides this care. In most instances, this requires participation between trauma surgeons and critical care specialists, as well as trauma and critical care services. With proper leadership and systems to ensure effective communication between such services, these goals can be achieved. Important secondary goals, in education and research, can also be achieved by such methods. Rather than further fractionate the care of patients, who frequently need 24-hour physician coverage and involvement of people with many different specialty areas of knowledge, it is crucial that an effective, cooperative system be designed for each institution that provides this care.