A safety assessment of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of hemorrhagic, hypovolemic shock.

OBJECTIVE: To determine the safety and possible efficacy of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of patients in Class II-IV hemorrhagic, hypovolemic shock. DESIGN: Multicenter, randomized, normal saline-controlled, dose-escalation study. SETTING: Eleven hospitals in the U.S. and Belgium. SUBJECTS: One hundred and thirty-nine (139) hospitalized patients with Class II-IV hemorrhagic, hypovolemic shock within the previous 4 hours who still were requiring therapy for shock. INTERVENTIONS: Beginning with the lowest dose, patients were randomized to receive 50, 100, or 200 mL of either 10% DCLHb or normal saline infused intravenously over 15 minutes. Following infusion of either treatment, further fluid resuscitation could be given, as necessary, to maintain perfusion. Vital signs, laboratory assessments, blood and fluid administration, complications, and adverse events were recorded at various times from the end of infusion through 72 hours after infusion. RESULTS: A total of 29 (13 DCLHb- and 16 saline-treated) patients died during the study period. Adverse events were experienced by 61% of patients in the DCLHb group and 53% of patients in the saline group; serious adverse events occurred in 28% of DCLHb-treated patients and 30% of saline-treated patients. The incidence of prospectively defined, clinical complications, including renal insufficiency and renal failure, was similar between the treatment groups except for the occurrence of dysrhythmias/conduction disorders, which occurred significantly more frequently in the saline-treated patients than the DCLHb-treated patients (p = 0.041). At the highest dose level (200 mL), statistically significant between-group differences were observed with greater increases in serum amylase, LDH, the isoenzymes LD1,2,4 and 5, and CK-MB in the DCLHb group compared to the control group; none were of clinical significance. The volume of blood administered did not differ between the groups. Overall 24- and 72-hour survival rates were similar between treatment groups, although the hospital discharge rate was slightly higher in the DCLHb-treated patients (80%) compared with the saline-treated patients (74%). CONCLUSION: Administration of 50 to 200 mL of DCLHb to patients in hemorrhagic, hypovolemic shock was not associated with evidence of end organ toxicity or significant adverse events. Further studies involving larger doses and, perhaps, earlier administration of DCLHb are warranted.

Fluid replacement for hypotensive injury victims: how, when and what risks?

Intravenous fluid administration is considered universally indicated for patients with post-traumatic hypotension of presumed hemorrhagic origin, regardless of the mechanism of injury, anatomic location, and whether hemostasis has been achieved. This premise is based primarily on animal studies in which blood loss results from a controlled catheter withdrawal. However, more recent hemorrhage models that incorporate a vascular injury, as well as recently completed clinical trials, have indicated that attempts to restore blood pressure before surgical hemostasis may have the undesirable effects of accentuating hemorrhage and mortality.

Research directions in emergency medicine.

The goal of emergency medicine is to improve health while preventing and treating disease and illness in patients seeking emergency medical care. Improvements in emergency medical care and the delivery of this care can be achieved through credible and meaningful research efforts. Improved delivery of emergency medical care through research requires careful planning and the wise use of limited resources. To achieve this goal, emergency medicine must provide appropriate training of young investigators and attract support for their work. Promotion of multidisciplinary research teams will help the specialty fulfill its goals. The result will be the improvement of emergency medical care which will benefit not only the patients emergency physicians serve but also, ultimately, the nation's health.

Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries.

BACKGROUND: Fluid resuscitation may be detrimental when given before bleeding is controlled in patients with trauma. The purpose of this study was to determine the effects of delaying fluid resuscitation until the time of operative intervention in hypotensive patients with penetrating injuries to the torso. METHODS: We conducted a prospective trial comparing immediate and delayed fluid resuscitation in 598 adults with penetrating torso injuries who presented with a pre-hospital systolic blood pressure of < or = 90 mm Hg. The study setting was a city with a single centralized system of pre-hospital emergency care and a single receiving facility for patients with major trauma. Patients assigned to the immediate-resuscitation group received standard fluid resuscitation before they reached the hospital and in the trauma center, and those assigned to the delayed-resuscitation group received intravenous cannulation but no fluid resuscitation until they reached the operating room. RESULTS: Among the 289 patients who received delayed fluid resuscitation, 203 (70 percent) survived and were discharged from the hospital, as compared with 193 of the 309 patients (62 percent) who received immediate fluid resuscitation (P = 0.04). The mean estimated intraoperative blood loss was similar in the two groups. Among the 238 patients in the delayed-resuscitation group who survived to the postoperative period, 55 (23 percent) had one or more complications (adult respiratory distress syndrome, sepsis syndrome, acute renal failure, coagulopathy, wound infection, and pneumonia), as compared with 69 of the 227 patients (30 percent) in the immediate-resuscitation group (P = 0.08). The duration of hospitalization was shorter in the delayed-resuscitation group. CONCLUSIONS: For hypotensive patients with penetrating torso injuries, delay of aggressive fluid resuscitation until operative intervention improves the outcome.

Resuscitation of canine hemorrhagic hypotension with large-volume isotonic crystalloid: impact on lung water, venous admixture, and systemic arterial oxygen saturation.

The objective of this study was to test the hypothesis that after hemorrhagic hypotension, reinfusion of the shed blood with threefold that volume of lactated Ringer's (LR) solution will significantly increase lung water and venous admixture and hence decrease systemic arterial oxygen saturation. A prospective, randomized, fixed-volume hemorrhage laboratory study was performed at the Oklahoma University Health Sciences Center on 18 anesthetized mongrel dogs. After 40 mL/kg of blood were withdrawn through a femoral artery catheter, the dogs were randomized either to the control group (n = 9) that received a reinfusion of the shed blood, or to the LR treatment group (n = 9) that received an intravenous mixture of the shed blood with 120 mL/kg of LR. After fluid resuscitation, pulmonary artery occlusion pressure (PAOP) and cardiac output (CO) were significantly increased in the LR group compared with control animals (PAOP, 18.7 +/- 1.1 vs 13.4 +/- 2.9 mm Hg; CO, 8.14 +/- 1.08 vs 4.59 +/- 0.47 L/min; P < .05 each). However, lung water, venous admixture, and systemic arterial PO2 were similar between groups. In this fixed-volume hemorrhage model, hemodiluting the reinfused shed blood with threefold the volume of LR did not significantly influence lung water, venous admixture, or systemic arterial oxygen saturation.

Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: a preliminary report.

Although intravenous (IV) fluid therapy is routinely prescribed for hypotensive injury victims, there are concerns that elevating the blood pressure before hemorrhage is controlled may be detrimental. This is a preliminary report of an ongoing randomized study designed to evaluate the effect fluid resuscitation, delayed until surgical intervention, has on the outcome for hypotensive victims of penetrating truncal injury. In the first year, 300 consecutive patients with gunshot or stab wounds to the trunk who had a systolic blood pressure of 90 mm Hg or less were entered into the study. Patients were excluded from the outcome analysis because of death at the scene or minor injury not requiring surgical intervention. The remaining study patients were randomized into (1) an immediate resuscitation group (n = 96) for whom IV fluid resuscitation was initiated in the ambulance and in the emergency center before surgical intervention, or (2) a delayed resuscitation group (n = 81) for whom IV fluid resuscitation was delayed until the time of surgical intervention. The two study groups were found to be well balanced with respect to anatomic injury severity, pretreatment vital signs, survival probability, and preoperative treatment times. There were no significant differences in the rate of survival to hospital discharge (immediate resuscitation group, 56%; delayed resuscitation group, 69%). There were no significant differences in the rate of postoperative complications. Further study is necessary to determine if it is advantageous to delay fluid resuscitation until surgical intervention.

Use of hypertonic saline/dextran versus lactated Ringer's solution as a resuscitation fluid after uncontrolled aortic hemorrhage in anesthetized swine.

STUDY OBJECTIVE: We tested the hypothesis that following aortotomy, administration of hypertonic saline/dextran increases hemorrhage and mortality. We also compared hypertonic saline/dextran with the standard therapy of attempting to replace three times the amount of lost blood with lactated Ringer's solution. DESIGN: In this model of uncontrolled arterial hemorrhage resulting from aortotomy, 24 anesthetized Yorkshire swine underwent splenectomy, stainless steel wire placement in the infrarenal aorta, and instrumentation with Swan-Ganz and carotid artery catheters. The wire was pulled, producing a 5-mm aortotomy and spontaneous intraperitoneal hemorrhage. INTERVENTIONS: The animals were randomly assigned to one of three study groups: control; hypertonic saline/dextran group in which six minutes after aortotomy a 4-mL/kg mixture of IV 7.5% NaCl and 6% Dextran-70 was given over one minute; or lactated Ringer's group in which six minutes after aortotomy 80 mL/kg IV lactated Ringer's was given over nine minutes. MEASUREMENTS AND MAIN RESULTS: The volume of hemorrhage and the mortality rate in hypertonic saline/dextran-treated animals were significantly greater than in the nonresuscitated controls (1,340 +/- 230 mL versus 783 +/- 85 mL and five of eight versus zero of eight, respectively; P less than .05). Although the mortality rate in the lactated Ringer's group was not significantly different from the hypertonic saline/dextran group, survival time was significantly shorter than in the hypertonic saline/dextran group. CONCLUSION: In this model of uncontrolled hemorrhage, immediate IV administration of hypertonic saline/dextran significantly increased hemorrhage volume and mortality. However, the accentuation of hemorrhage and reduction in survival were not as great as that produced by the standard practice of attempting to replace the lost blood with three times that volume of lactated Ringer's.

Community hospital level II trauma center outcome.

Currently, level II trauma center standards allow trauma surgeons to take call out-of-hospital. To address the concern that this practice may adversely influence outcome, we tested the hypothesis that the survival of injury victims treated at a level II trauma center is significantly different from that predicted by the Major Trauma Outcome Study (MTOS). In addition, we examined the impact of trauma surgeons taking call out-of-hospital on the survival of patients with severe thoracoabdominal injury. Over a 26-month period, a total of 3,689 consecutive injured patients who were treated at a community hospital level II trauma center were entered into this study. There was no significant difference between the MTOS survival and the actual survival in the overall population (96% vs. 97%, respectively; Z statistic = ns). Among the patients with severe thoracoabdominal injury (i.e., Abbreviated Injury Scale score greater than or equal to 3), there was no significant difference in survival between the patients whose arrival time corresponded to the presence of an in-hospital surgeon (0700-1800 hours) versus those who arrived when a surgeon was generally out-of-hospital (1801-0659 hours), (76% vs. 81%, respectively; p = ns). From these data we conclude that there was no significant difference between the survival observed and that predicted by the MTOS at our community hospital, which complies with level II trauma center standards. Furthermore, in the cohort with severe thoracoabdominal injury, the response of trauma surgeons from out-of-hospital did not adversely influence survival.

The detrimental effects of intravenous crystalloid after aortotomy in swine.

We tested the hypothesis that, after aortotomy, rapidly replacing three times the blood volume deficit with intravenous crystalloid will increase hemorrhage and decrease survival. Sixteen anesthetized Yorkshire swine underwent splenectomy and stainless steel wire placement in the infrarenal aorta and were instrumented with pulmonary artery and carotid artery catheters. The wire was pulled, producing a 5 mm aortotomy and spontaneous intraperitoneal hemorrhage. The animals had been alternately assigned to either an untreated control group (n = 8) or a treatment group (n = 8), which received 80 ml/kg lactated Ringer's solution intravenously. The volume of hemorrhage and the mortality rate were significantly increased (p less than 0.05) in the treatment group receiving lactated Ringer's solution relative to the control animals (2142 +/- 178 ml versus 783 +/- 85 ml, and eight of eight animals versus zero of eight animals, respectively). From these data we conclude that, in this model of uncontrolled arterial hemorrhage resulting from abdominal aortotomy, rapidly administering lactated Ringer's solution intravenously significantly increases hemorrhage and death.

Hemodynamic response to abdominal aortotomy in the anesthetized swine.

This study was conducted to determine the hemodynamic response to uncontrolled hemorrhage following aortotomy in anesthetized swine. Eight Yorkshire swine underwent splenectomy and stainless steel wire placement in the anterior infrarenal aorta and were instrumented with Swan-Ganz and carotid artery catheters. Following an equilibration period, the wire was pulled. This produced a 5 mm aortotomy and spontaneous intraperitoneal hemorrhage. Serial measurements of mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), and cardiac output (CO) were obtained. From baseline to 5 min after aortotomy, there was a profound decrease in MAP in conjunction with a significant decrease in CO and MPAP. After the initial 5 min period, there was a progressive elevation in MAP, CO, and MPAP. Peripheral vascular resistance (PVR) was significantly decreased after aortotomy and returned to baseline after 60 min. From these data, we conclude that aortotomy produces a rapid depression and spontaneous recovery in MAP, CO, and MPAP. Aortotomy also produces a significant decrease in PVR, which is not generally associated with hemorrhagic hypotension.

Effects of pneumatic antishock garment inflation in normovolemic subjects.

This study examines the effects of inflation of pneumatic antishock garments (PASG) in 10 normovolemic men (mean age 44 +/- 6 yr) undergoing diagnostic catheterization. Seven subjects had normal heart function and no evidence of coronary artery disease (CAD); three patients had CAD. High-fidelity multisensor catheters were employed to simultaneously record right and left heart pressures before PASG inflation and after inflation to 40, 70, and 100 mmHg. A thermal dilution catheter was used to obtain pulmonary capillary wedge pressure and cardiac output. Counterpressure increases greater than or equal to 40 mmHg were associated with significant changes in left and right heart pressures. Right and left ventricular end-diastolic pressures increased 100% (P less than 0.01); mean pulmonary arterial and aortic pressures increased 77 and 25%, respectively (P less than 0.01); systemic vascular resistance increased 22% (P less than 0.05) and pulmonary vascular resistance did not change in normal subjects at maximum PASG inflation. Heart rate, cardiac output, and aortic and pulmonary arterial pulse pressures did not change during inflation in either group. Right and left ventricular end-diastolic pressures and pulmonary capillary wedge pressure were greater (P less than 0.05) in the CAD group compared with the normal subjects during PASG inflation. The data suggest that the primary mechanism whereby PASG inflation induces changes in central hemodynamics in normovolemic subjects is through an acute increase in left ventricular afterload. PASG changes in afterload and pulmonary capillary wedge pressure imply that these devices should be used with caution in patients with compromised cardiac function.

Randomized trial of pneumatic antishock garments in the prehospital management of penetrating abdominal injuries.

Experimental data have suggested that pneumatic external counterpressure improves outcome in intra-abdominal hemorrhage by either a tamponade effect and/or elevation in central systemic blood pressure. As a result, the empiric use of the pneumatic antishock garment (PASG) has become a standard of care, even to the point where the device has been legislated as required equipment on emergency medical rescue vehicles. However, the effect of the PASG on intra-abdominal hemorrhage has not been evaluated in randomized clinical trials. The purpose of this study was to evaluate the effect of the PASG on the survival of hypotensive patients with penetrating abdominal injuries. During a 2 1/2-year period, 201 consecutive patients presenting with penetrating anterior abdominal injuries and an initial prehospital systolic blood pressure of 90 mm Hg or less were entered into the study. All prehospital care was delivered by the same municipal emergency medical services system, and all patients subsequently were transported to the same regional trauma facility. The patients were randomized into control and pneumatic external counterpressure groups by an alternate-day assignment of PASG use. The resulting study populations (control, n = 104; PASG, n = 97) were found to be well matched for survival probability indices, prehospital response and transport times, and the volume of IV fluids received. The results demonstrated no significant difference in the survival rates of the control and PASG treatment groups (81 of 104 vs 67 of 97). From these data we conclude that, contrary to previous claims, the PASG provides no significant advantage in improving survival in the urban prehospital management of penetrating abdominal injuries.

The relationship between total prehospital time and outcome in hypotensive victims of penetrating injuries.

Most authorities in the field of trauma recommend that seriously injured patients be transported directly to a regional trauma center, even if it requires bypassing nearby community hospitals. The purpose of our study was to examine the relationship between the survival rates of patients with presumed hemorrhagic shock due to penetrating injuries and the total prehospital time required to manage and deliver those patients to a single regional trauma center in a large urban area. During a 30-month-period, 498 consecutive victims of penetrating injury, presenting in the field with a systolic blood pressure of 90 mm Hg or less and transported to a single regional trauma center, were prospectively evaluated in terms of age; initial prehospital trauma score; injury severity score (ISS); TRISS probability of survival; response, scene, transport, and total prehospital times; and survival (discharge from hospital). All patients were managed and transported by a single urban paramedic service that has a fairly uniform response time (5.3 +/- 3 min) throughout its entire service area. The response area is spread out over an approximately 1,000 square-mile region, and transport times to the regional trauma center can exceed a half hour. The total prehospital time (TPT) was calculated as the time elapsed from the receipt of the emergency call to the time of arrival at the regional trauma center. Patients arbitrarily were categorized into four subsets according to the initial prehospital trauma score (1, 2 to 6, 7 to 11, 12 to 15). Patients also were analyzed in terms of four incremental groups of increasing TPT (0-20, 21-30, 31-40, greater than 40 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective randomized evaluation of antishock MAST in post-traumatic hypotension.

During an 18-month period, among 35,000 injured patients presenting to an urban trauma center, more than 3,500 were admitted, and 1,500 underwent surgery on the General Surgical Service. Three hundred fifty-two patients with prehospital systolic blood pressures of less than 90 mm Hg were randomized on an alternate day basis to receive treatment with 'MAST' (163 patients) or 'No-MAST' (189 patients). Age, mechanism of injury, prehospital management times, prehospital trauma scores, prehospital fluids administered, Injury Severity Scores, emergency center treatment, operative protocol, and calculated probability of survival were virtually identical for both groups. Eighty-eight per cent of the injuries were produced by penetrating wounds. The predominant injury area was the abdomen in 40%, the thorax in 37%, and the extremities in 13%. There was no statistically significant difference in evaluation and outcome data between the groups. Within a controlled catchment, only 2.5% of injured patients and 22% of those undergoing operation qualified for prehospital use of MAST. We conclude that for penetrating trauma with prehospital times of 30 minutes or less, MAST provide no advantage with regard to survival, length of hospital stay, or reduced hospital costs.

Hemodynamic response to rapid pneumatic antishock garment deflation.

Irreversible hypotension with subsequent cardiovascular collapse has been reported as a catastrophic complication of inappropriate pneumatic antishock garment (PASG) deflation. This study was undertaken to analyze the cardiodynamic response by which PASG deflation produces hypotension. Five normovolemic patients undergoing cardiac catheterization for atypical chest pain syndrome volunteered for this study. Serial measurements of right atrial, right ventricular, pulmonary artery, left ventricular, and aortic pressures were obtained with subjects supine at the following times: prior to inflation of the PASG; during PASG inflation at 100 mm Hg; and during rapid PASG deflation. Pulmonary and aortic flow velocities were recorded in two patients. The application of external pressure with PASG produced a significant increase in left and right heart pressures (P less than .05). Sudden PASG deflation produced significant transient hypotensive changes (P less than .01). When PASG deflation hemodynamics were compared to preinflation data, mean arterial pressure decreased 14 mm Hg (P less than .01); mean pulmonary pressure decreased 6 mm Hg (P less than .01); and mean right atrial and left ventricular end-diastolic pressures decreased 4 and 6 mm Hg, respectively (P less than .01). An analysis of right and left heart hemodynamic data suggests that the early hypotensive response associated with PASG deflation is consistent with a reduction in left ventricular afterload followed by a decrease in preload.

Effect of antishock trousers on the trauma score: a prospective analysis in the urban setting.

This study was designed to determine the effect of military antishock trousers (MAST) use on the presenting emergency center trauma score (TS) in an urban prehospital setting. Sixty-eight patients were assigned randomly to study and control groups in a prospective investigation of the use of MAST on injured patients with hypotension. Thirty-two control patients, whose mean initial systolic BP was 59 +/- 32 mm Hg, and 36 MAST-treated patients, whose mean initial BP was 55 +/- 31 mm Hg, were found to be well matched for age; sex; type and location of injuries; initial field TS; response, field management, and transport times; and the total amount of intravenous crystalloid infused. Our results demonstrated no significant difference between the control and MAST-treated groups in the presenting emergency department TS (9.8 +/- 6.6 vs 10.6 +/- 5.9). These data conflict with the widely accepted belief that MAST will always enhance conventional support for improving the prehospital condition of injured patients with significant hypotension.

Military antishock trousers in a patient with adrenergic-resistant anaphylaxis.

The case presented concerns a patient taking propranolol who developed a severe anaphylactic reaction to pollen extract immunotherapy. Although the hypotension that occurred during the anaphylaxis was refractory to intravenous fluids, epinephrine, and dopamine, the antishock trouser suit was effective in elevating blood pressure.