Biomedical subjects

Martin A Schreiber

Publications and source records attributed to Martin A Schreiber.

15 recordsLinked to original sources

PubMed2006

Risk factors for respiratory failure following operative stabilization of thoracic and lumbar spine fractures.

BACKGROUND: Respiratory failure is a serious complication that can adversely affect the hospital course and survival of multiply injured patients. Some studies have suggested that delayed surgical stabilization of spine fractures may increase the incidence of respiratory complications. However, the authors of these studies analyzed small sets of patients and did not assess the independent effects of multiple risk factors. METHODS: A retrospective cohort study was conducted at a regional level-I trauma center to identify risk factors for respiratory failure in patients with surgically treated thoracic and lumbar spine fractures. Demographic, diagnostic, and procedural variables were identified. The incidence of respiratory failure was determined in an adult respiratory distress syndrome registry maintained concurrently at the same institution. Univariate and multivariate analyses were used to determine independent risk factors for respiratory failure. An algorithm was formulated to predict respiratory failure. RESULTS: Respiratory failure developed in 140 of the 1032 patients in the study cohort. Patients with respiratory failure were older; had a higher mean Injury Severity Score (ISS) and Charlson Comorbidity Index Score; had greater incidences of pneumothorax, pulmonary contusion, and thoracic level injury; had a lower mean Glasgow Coma Score (GCS); were more likely to have had a posterior surgical approach; and had a longer mean time from admission to surgical stabilization than the patients without respiratory failure (p < 0.05). Multivariate analysis identified five independent risk factors for respiratory failure: an age of more than thirty-five years, an ISS of > 25 points, a GCS of < or = 12 points, blunt chest injury, and surgical stabilization performed more than two days after admission. An algorithm was created to determine, on the basis of the number of preoperative predictors present, the relative risk of respiratory failure when surgery was delayed for more than two days. CONCLUSIONS: Independent risk factors for respiratory failure were identified in an analysis of a large cohort of patients who had undergone operative stabilization of thoracic and lumbar spine fractures. Early operative stabilization of these fractures, the only risk factor that can be controlled by the physician, may decrease the risk of respiratory failure in multiply injured patients.

Adult↗

PubMed2005

Preclinical trauma studies of recombinant factor VIIa.

Preclinical studies in animals and ex vivo human blood have provided a solid rationale for conducting prospective randomized trials in trauma patients. Small animal models have been utilized to study the efficacy of recombinant activated factor VII (rFVIIa; NovoSeven) in treating thrombocytopenic rabbits and for the reversal of anticoagulation. Safety models in the rabbit also exist to test for systemic activation of clotting and pathologic thrombosis. Animal models simulating traumatic injuries in humans have primarily been performed in pigs because of species similarities in terms of coagulation characteristics and the larger internal organs. The pig studies, utilizing human rFVIIa, have shown increased strength of clot formation, decreased bleeding, and improved survival. However, these findings are not uniform and are dependant on the model chosen. All of the animal models described have provided good safety data and suggest that the use of rFVIIa is not associated with systemic activation of coagulation or microthrombosis of end organs.

Animals↗

PubMed2005

Correlation of central venous and arterial blood gas measurements in mechanically ventilated trauma patients.

HYPOTHESIS: Central venous blood gas (VBG) measurements of pH, PCO2, and base excess can be substituted for the same values obtained from an arterial blood gas (ABG) analysis in mechanically ventilated trauma patients, obviating the need for arterial puncture. DESIGN AND SETTING: Prospective comparison of 99 sets of VBGs and ABGs at a level 1 academic trauma center. PATIENTS: A consecutive sample of 25 trauma patients admitted to the intensive care unit who required mechanical ventilation and had both central venous and arterial catheters. MAIN OUTCOME MEASURES: Pearson correlations and Bland-Altman limits of agreement (LOAs) for pH, PCO2, and base excess values from each set of VBGs and ABGs. RESULTS: When VBG and ABG values were compared, pH had R = 0.92, P<.001, and 95% LOAs of -0.09 to 0.03; PCO2, R = 0.88, P<.001, and 95% LOAs of -2.2 to 10.9; and base excess, R = 0.96, P<.001, and 95% LOAs of -2.2 to 1.8. A receiver operating characteristic curve showed that a central venous PCO2 of 50 mm Hg had 100% sensitivity and 84% specificity for determining significant hypercarbia (arterial PCO2 > 50 mm Hg). CONCLUSIONS: Central venous and arterial PCO2, pH, and base excess values correlate well, but their LOAs represent clinically significant ranges that could affect management. Although VBGs cannot be substituted for ABGs in mechanically ventilated trauma patients during the initial phases of resuscitation, clinically reliable conclusions can be reached with VBG analysis.

Blood Gas Analysis↗

PubMed2005

Coagulopathy in the trauma patient.

PURPOSE OF REVIEW: Homeostasis represents a delicate balance between hemostatic and fibrinolytic processes. This balance permits arrest of hemorrhage after mild injury but prevents thrombosis from occurring under normal circumstances. Trauma disturbs the equilibrium between hemostatic and fibrinolytic processes, frequently producing either a hypocoagulable state or a hypercoagulable state depending on the severity of injury, degree of hemorrhage, and the nature of the resuscitation. The purpose of this review is to describe the epidemiology and pathophysiology of coagulopathy after trauma and to discuss novel methods of treating it. RECENT FINDINGS: Published reports during the past year focus on the pathophysiology of coagulopathy after trauma and novel methods of treatment. Individual effects of hypothermia and acidosis on clotting factors and platelet function have been described. The effects of varying resuscitation fluids on coagulopathy have also been described as well as the course of coagulopathy over time. Recombinant factor VIIa has emerged as a popular therapy for traumatic coagulopathy although a prospective randomized trial has yet to be published. The efficacy of several new dressings for the local control of hemorrhage has been reported. SUMMARY: Changes in coagulation following trauma are characterized by a complex series of events that may result in either a hypocoagulable or a hypercoagulable state. Routinely analyzed coagulation parameters do not adequately describe this state and they are deficient for guiding its therapy. Several promising new agents are available for treating hemorrhage in coagulopathic trauma patients that should result in improved survival.

Disseminated Intravascular Coagulation↗

PubMed2005

Hypercoagulability is most prevalent early after injury and in female patients.

BACKGROUND: Hypercoagulability after injury is a major source of morbidity and mortality. Recent studies indicate that there is a gender-specific risk in trauma patients. This study was performed to determine the course of coagulation after injury and to determine whether there is a gender difference. We hypothesized that hypercoagulability would occur early after injury and that there would be no difference between men and women. METHODS: This was a prospective cohort study. Inclusion criteria were admission to the intensive care unit, Injury Severity Score > 4, and the ability to obtain consent from the patient or a relative. A Thrombelastograph (TEG) analysis was performed and routine coagulation parameters and thrombin-antithrombin complexes were measured within 24 hours of injury and then daily for 4 days. RESULTS: Sixty-five patients met criteria for entry into the study. Their mean age was 42 +/- 17 years and their mean Injury Severity Score was 23 +/- 12. Forty patients (62%) were men. The prevalence of a hypercoagulable state by TEG was 62% on day 1 and 26% on day 4 (p < 0.01). Women were significantly more hypercoagulable on day 1 than men as measured by the time to onset of clotting (women, 2.9 +/- 0.7 minutes; men, 3.9 +/- 1.5 minutes; p < 0.01; normal, 3.7-8.3 minutes). Mean platelet counts, international normalized ratios, and partial thromboplastin times were within normal limits throughout the study. Thrombin activation as measured by thrombin-antithrombin complexes decreased from 34 +/- 15 microg/L on day 1 to 18 +/- 8 microg/L (p < 0.01) on day 4, consistent with the prevalence of hypercoagulability by TEG. CONCLUSION: Hypercoagulability after injury is most prevalent during the first 24 hours. Women are more hypercoagulable than men early after injury. The TEG is more sensitive than routine coagulation assays for the detection of a hypercoagulable state.

Adult↗

PubMed2005

Hextend attenuates hypercoagulability after severe liver injury in swine.

BACKGROUND: Hypercoagulability is a major source of morbidity and mortality after injury. A resuscitation regimen that modulates this coagulopathy may prove beneficial. We sought to evaluate the effects of lactated Ringer's (LR) solution and Hextend on the resuscitation of uncontrolled hemorrhagic shock. METHODS: Twenty swine underwent invasive line placement, midline celiotomy, and splenectomy. After a 15-minute stabilization period, we recorded a baseline mean arterial pressure and created a grade V liver injury. The animals bled freely for 30 minutes, after which we measured the initial blood loss (that after injury). We blindly randomized the swine to receive LR solution or Hextend to achieve and maintain the baseline mean arterial pressure for 90 minutes postinjury. Laboratory values were obtained at baseline and on completion of the 2-hour study period. RESULTS: The initial blood loss (before resuscitation) was 22 mL/kg in both treatment groups (p = 0.97). Animals required 119 +/- 78 mL/kg of fluid in the LR group and 40 +/- 21 mL/kg in the Hextend group (p = 0.01). After resuscitation, the secondary blood loss was 3.7 +/- 1.7 mL/kg in the LR group and 4.7 +/- 1.1 mL/kg in the Hextend group (p = 0.1). Thrombelastography revealed a hypercoagulable state in all animals after injury. This was less pronounced in those animals resuscitated with Hextend. Routine tests of coagulation did not reveal a hypercoagulable state. CONCLUSION: Modulation and restoration of normal coagulation is critical in the management of trauma patients. The patient's coagulation profile might determine the type of fluid to be used at various times during their course. Thrombelastography is superior to routine coagulation assays for the detection of a hypercoagulable state. Resuscitation with Hextend results in a decreased fluid requirement and attenuation of hypercoagulability after injury without increased blood loss.

Animals↗

PubMed2004

Damage control surgery.

Damage control is a staged approach to severely injured patients predicated on treatment priorities. Initially, life-threatening injuries are addressed expediently, and procedures are truncated. Normal physiology is restored in the ICU, and patients subsequently are returned to the operating room for definitive management. This strategy breaks the bloody vicious cycle and results in improved outcomes. Novel technologies like CAVR and rFVIIa contribute to the effectiveness of damage control.

Acidosis↗

PubMed2004

Resuscitation with lactated ringer's does not increase inflammatory response in a Swine model of uncontrolled hemorrhagic shock.

Lactated Ringer's (LR) and normal saline (NS) are widely and interchangeably used for resuscitation of trauma victims. Studies show LR to be superior to NS in the physiologic response to resuscitation. Recent in vitro studies demonstrate equivalent effects of LR and NS on leukocytes. We aimed to determine whether LR resuscitation would produce an equivalent inflammatory response compared with normal saline (NS) resuscitation in a clinically relevant swine model of uncontrolled hemorrhagic shock. Thirty-two swine were randomized. Control animals (n = 6) were sacrificed following induction of anesthesia for baseline data. Sham animals (n = 6) underwent laparotomy and 2 h of anesthesia. Uncontrolled hemorrhagic shock animals (n = 10/group) underwent laparotomy, grade V liver injury, and blinded resuscitation with LR or NS to maintain baseline blood pressure for 1.5 h before sacrifice. Lung was harvested, and tissue mRNA levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-alpha) were determined using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR). Sections of lung were processed and examined for neutrophils sequestered within the alveolar walls. Cytokine analysis showed no difference in IL-6 gene transcription in any group (P = 0.99). Resuscitated swine had elevated G-CSF and TNF-alpha gene transcription, but LR and NS groups were not different from each other (P= 0.96 and 0.10, respectively). Both resuscitation groups had significantly more alveolar neutrophils present than controls (P < 0.01) and shams (P < 0.05) but were not different from one another (P= 0.83). LR and NS resuscitation have equivalent effects on indices of inflammation in the lungs in our model of uncontrolled hemorrhagic shock.

Animals↗

PubMed2003

Amplification of the proinflammatory transcription factor cascade increases with severity of uncontrolled hemorrhage in swine.

INTRODUCTION: Hypotension causes diffuse liver injury accompanied by increased local production of interleukin-6 (IL-6) in swine models of uncontrolled hemorrhagic shock (HS). IL-6 is transcriptionally up-regulated by nuclear factor (NF)-kappaB and results in activation of signal transducer and activator of transcription-3 (Stat3) in a murine model of controlled HS. Our objectives were: 1). to determine if increased IL-6 production and NF-kappaB and Stat3 activation occurs in a swine model of uncontrolled HS, and 2). to assess whether or not levels of IL-6 mRNA and activity of NF-kappaB and Stat3 correlate with shock severity. MATERIALS AND METHODS: Swine were assigned to four groups: 1). control animals (n = 6): no intervention, 2). sham operation (n = 6): celiotomy and splenectomy, 3). uncontrolled hemorrhagic shock (UHS) (n = 6): sham plus grade V vascular liver injury and resuscitation, 4). profound uncontrolled hemorrhagic shock (PUHS) (n = 8): UHS after dilutional hypothermia. Following euthanasia at 2 h, livers were harvested, total RNA isolated, and IL-6 mRNA levels quantified by Q-RT-PCR (ABI Prism 7700, Applied Biosystems International, Foster City, CA). Protein was extracted for measurement of NF-kappaB and Stat3 activity by electrophoretic mobility shift assay (EMSA). RESULTS: Compared to shams, IL-6 mRNA levels increased 4.5-fold in UHS and 90-fold in PUHS (P < 0.001). Compared with shams; NF-kappaB activity increased 2-fold in both UHS and PUHS (P < 0.05). Stat3 activity was equivalent (not significant) in UHS when compared with shams but increased 5.3-fold in PUHS. (P < 0.05). CONCLUSION: These findings suggest that regional proinflammatory cytokine production results from and perpetuates a proinflammatory transcription factor cascade in a swine model of uncontrolled hemorrhagic shock and indicate that this process is proportional to the severity of shock.

Animals↗

PubMed2003

The effect of recombinant factor VIIa on noncoagulopathic pigs with grade V liver injuries.

BACKGROUND: Recombinant Factor VIIa (rFVIIa) has been used to decrease bleeding in a number of settings, including hemophilia, liver transplantation, intractable bleeding, and cirrhosis. It has also been shown to reduce bleeding in coagulopathic pigs with Grade V liver injuries when used as an adjunct to packing. This study was performed to determine if rFVIIa would reduce blood loss after a Grade V liver injury in noncoagulopathic pigs when used as sole therapy. STUDY DESIGN: Thirty normothermic animals were randomized to receive either 150 microg/kg of rFVIIa or normal saline intravenously. After laparotomy and splenectomy, a standardized Grade V liver injury was made with a liver clamp. Thirty seconds after injury, blinded therapy was given. Blood loss was measured 15 minutes after injury and the abdomen was closed. Animals were resuscitated to their baseline blood pressure and the study was continued for 2 hours. Serial coagulation parameters were obtained. Following the study period, blood loss was measured and an autopsy was performed. Grossly normal areas of lung were examined for evidence of intravascular thrombosis. RESULTS: Mean Factor VII:C levels increased 155-fold in the treatment group after infusion of rFVIIa. The mean prothrombin time in the treatment group decreased from 9.8 +/- 0.4 seconds to 7.3 +/- 0.2 seconds and remained significantly different from the control group throughout the study (p < 0.01). There were no differences in other coagulation parameters. Mean initial blood loss was 822 +/- 266 mL in the treatment group and 768 +/- 215 mL in the control group (p = 0.6). Rebleeding blood volume was 397 +/- 191 mL in the treatment group and 437 +/- 274 mL (p = 0.6) in the control group. Lung histology revealed no evidence of abnormal microvascular thrombosis. CONCLUSIONS: rFVIIa does not reduce blood loss after Grade V liver injury when it is used as sole therapy in warm noncoagulopathic pigs.

Animals↗

PubMed2002

Military trauma training performed in a civilian trauma center.

BACKGROUND: In 1996, Congress passed legislation requiring the Department of Defense to conduct trauma training in civilian hospitals. In September of 1998 an Army team composed of surgeons, nurses, emergency medical technicians (EMTs), and operating room technicians (OR techs) trained in a civilian level 1 trauma center. This study analyzes the quality of the training. METHODS: The training period was 30 days. Before and after training all members completed a questionnaire of their individual and team ability to perform at their home station, at the civilian hospital, and in the combat setting. Surgeons maintained an operative log, which was compared with their prior year's experience. Primary trauma cases (PTCs) met Residency Review Committee criteria as defined category cases and were done acutely. Other personnel tracked the percentage of supporting soldier tasks (SSTs) they performed or were exposed to during the training period. RESULTS: Review of the questionnaires revealed a significant increase in confidence levels in all areas tested (P < 0.005). The three general surgeons performed a total of 42 PTCs during the 28 call periods, or 1.5 PTCs per call period. During the prior year, the same three general surgeons performed 20 PTCs during 114 call periods for 0.175 cases per call period (P = 0.003). The maximum number of PTCs performed during one call period at the civilian center was 4, compared with 5 PTCs performed by one Army surgeon during the Somalia 1993 mass casualty event. Performance of or exposure to SSTs was 71% for the EMTs, 94% for the nurses, and 79% for the OR techs. CONCLUSIONS: A 1-month training experience at a civilian trauma center provided military general surgeons with a greater trauma experience than they receive in 1 year at their home station. Other personnel on the team benefited by performing or being exposed to their SSTs. Further training of military teams in civilian trauma centers should be investigated.

Education↗

PubMed2002

Determinants of mortality in patients with severe blunt head injury.

CONTEXT: Head injury is the leading cause of traumatic death in the United States. HYPOTHESIS: A set of clinical parameters available soon after injury can be used to accurately predict outcome in patients with severe blunt head trauma. DESIGN: Validation cohort study. SETTING: Urban level I trauma center. PATIENTS AND METHODS: Data from patients with severe blunt head injury, as defined by inability to follow commands, were prospectively entered into a neurosurgical database and analyzed. The impact on survival of 23 potentially predictive parameters was studied using univariate analysis. Logistic regression models were used to control for confounding factors and to assess interactions between variables, whose significance was determined by univariate analysis. Goodness of fit was calculated with the Hosmer-Lemeshow c statistic. The predictability of the logistic model was evaluated by measuring the area under the receiver operating characteristic curve (AUC). RESULTS: Logistic regression analysis revealed that 5 risk factors were independently associated with death. These variables included systemic hypotension in the emergency department, midline shift on computed tomographic scan, intracranial hypertension, and absence of pupillary light reflex. A low Glasgow Coma Scale score and advanced age were found to be highly correlated risk factors that, when combined, were independently associated with mortality. The model showed acceptable goodness of fit, and the AUC was 80.5%. CONCLUSIONS: Systemic hypotension and intracranial hypertension are the only independent risk factors for mortality that can be readily treated during the initial management of patients with severe head injuries. When used together, Glasgow Coma Scale score and age are significant predictors of mortality.

Adolescent↗

PubMed2002

Immediate effects of dry needling and acupuncture at distant points in chronic neck pain: results of a randomized, double-blind, sham-controlled crossover trial.

To evaluate immediate effects of two different modes of acupuncture on motion-related pain and cervical spine mobility in chronic neck pain patients compared to a sham procedure. Thirty-six patients with chronic neck pain and limited cervical spine mobility participated in a prospective, randomized, double-blind, sham-controlled crossover trial. Every patient was treated once with needle acupuncture at distant points, dry needling (DN) of local myofascial trigger points and sham laser acupuncture (Sham). Outcome measures were motion-related pain intensity (visual analogue scale, 0-100 mm) and range of motion (ROM). In addition, patients scored changes of general complaints using an 11-point verbal rating scale. Patients were assessed immediately before and after each treatment by an independent (blinded) investigator. Multivariate analysis was used to assess the effects of true acupuncture and needle site independently. For motion-related pain, use of acupuncture at non-local points reduced pain scores by about a third (11.2 mm; 95% CI 5.7, 16.7; P = 0.00006) compared to DN and sham. DN led to an estimated reduction in pain of 1.0 mm (95% CI -4.5, 6.5; P = 0.7). Use of DN slightly improved ROM by 1.7 degrees (95% CI 0.2, 3.2; P = 0.032) with use of non-local points improving ROM by an additional 1.9 degrees (95% CI 0.3, 3.4; P = 0.016). For patient assessment of change, non-local acupuncture was significantly superior both to Sham (1.7 points; 95% CI 1.0, 2.5; P = 0.0001) and DN (1.5 points; 95% CI 0.4, 2.6; P = 0.008) but there was no difference between DN and Sham (0.1 point; 95% CI -1.0, 1.2; P = 0.8). Acupuncture is superior to Sham in improving motion-related pain and ROM following a single session of treatment in chronic neck pain patients. Acupuncture at distant points improves ROM more than DN; DN was ineffective for motion-related pain.

Acupuncture Analgesia↗

PubMed2002

The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries.

BACKGROUND: Recombinant factor VIIa (rFVIIa) has been used to decrease bleeding in a number of settings including hemophilia, liver transplantation, intractable bleeding, and cirrhosis. Experience in the trauma setting is limited. This study was performed to determine whether rFVIIa would reduce bleeding after a grade V liver injury in hypothermic, dilutionally coagulopathic pigs when used as an adjunct to abdominal packing and to determine whether increasing the dose of the drug increased its hemostatic efficacy. METHODS: Thirty animals were randomized to receive 180 microg/kg of rFVIIa, 720 microg/kg of rFVIIa, or vehicle buffer control. After laparotomy and splenectomy, animals underwent a 60% blood volume isovolemic exchange transfusion with 5% human albumin. The animals' temperature was maintained at 33 degrees C and a standardized grade V liver injury was made with a liver clamp. Thirty seconds after injury, the abdomen was packed with laparotomy sponges, resuscitation was initiated, and blinded therapy was given. Animals were resuscitated to their baseline mean arterial pressure and the study was continued for 2 hours. Serial coagulation parameters were measured at the temperature they were drawn. After the study period, surviving animals were killed, posttreatment blood loss was measured, and an autopsy was performed. RESULTS: Ten animals were randomized to each group. After administration of study drug, factor VII clotting activity (FVII:C) was higher in the 720 microg/kg group than in the 180 microg/kg group (p < 0.01). FVII:C was higher in both treatment groups than in the control group (p < 0.01). The mean prothrombin time was shorter in the treatment groups than in the control group (p < 0.05). Mean arterial pressure was lower in the control group than in the treatment groups throughout the study (p < 0.01). Mean blood loss was less in the treatment groups than in the control group (p = 0.03). Mortality was not different between groups. There were no differences between the groups that received rFVIIa in any measured parameters except for FVII:C. Liver injuries were similar between groups and there was no evidence of microthrombosis on lung histology. CONCLUSION: rFVIIa reduces blood loss in hypothermic, dilutionally coagulopathic pigs with grade V injuries when used as an adjunct to packing. Increasing the dose does not enhance the hemostatic effect.

Animals↗

PubMed2002

Base deficit does not predict mortality when secondary to hyperchloremic acidosis.

Base deficit has been established as a predictor of mortality and endpoint of resuscitation. We hypothesized that in a significant subset of surgical intensive care patients, base deficit is secondary to hyperchloremic acidosis, and that these patients experience lower mortality than those patients whose base deficits are secondary to other causes. Seventy-five consecutive surgical intensive care patients with base deficits greater than 2.0 were prospectively studied. The etiology of the patients' base deficits was determined by admission laboratory data. Patients were divided into those with hyperchloremic acidosis, and those with acidosis from other causes. Mortality within these groups was compared by Fisher's exact test. Thirty-seven patients (49.3%) had hyperchloremic acidosis. Thirty-three patients (46.7%) had lactic acidosis. Three patients (4%) had base deficits secondary to ketosis, and two patients (2.6%) had base deficits secondary to uremia. There were no significant differences in age, APACHE II scores, or volumes of resuscitation between the hyperchloremic group and the remaining patients. There were four deaths (10.8%) in the hyperchloremic group and thirteen deaths (34.2%) in the remaining patients (P = 0.03). Hyperchloremic acidosis resulted from resuscitation with lactated Ringer's solution in 18 (48.6%) of the hyperchloremic patients. Hyperchloremic acidosis is a common etiology of base deficit in the surgical intensive care unit. It is associated with lower mortality than base deficit secondary to other causes. Moreover, it is frequently induced following resuscitation with lactated Ringer's solution. Failure to properly diagnose this subset of acidotic patients may result in inappropriate clinical interventions due to the erroneous presumption of ongoing tissue hypoxia.

Acid-Base Equilibrium↗