Lactated Ringer's is superior to normal saline in the resuscitation of uncontrolled hemorrhagic shock

BACKGROUND: Normal saline (NS) and lactated Ringer's solution (LR) continue to be used interchangeably for the resuscitation of hemorrhagic shock in some institutions. We hypothesized that, aside from hyperchloremic acidosis, NS resuscitation would be similar to that of LR in a swine model of uncontrolled hemorrhage. METHODS: Twenty swine weighing a mean of 37 kg underwent invasive line placement, midline celiotomy, and splenectomy. After a 15-minute stabilization period, we recorded a baseline mean arterial pressure (MAP) and created a grade V liver injury. The animals bled freely for 30 minutes after which we measured blood loss. We blindly randomized the swine to receive NS (10 animals) versus LR (10 animals) to achieve and maintain the baseline MAP for 90 minutes postinjury. Laboratory values were obtained at baseline and upon completion of the 2-hour study period. RESULTS: Initial blood loss was 25 mL/kg in the NS group and 22 mL/kg in the LR group (p = 0.54). Animals required 256.3 +/- 145.4 mL/kg of fluid in the NS group as compared with 125.7 +/- 67.3 mL/kg in the LR group (p = 0.04). The urine output was higher in the NS group (46.6 +/- 39.5 mL/kg versus 18.9 +/- 12.9 mL/kg, p = 0.04). Upon study completion, the NS group had a significant hyperchloremia (119 +/- 1.9 mEq/L versus 105 +/- 2.9 mEq/L, p < 0.01) with acidosis (7.28 +/- 0.12 versus 7.45 +/- 0.06, p < 0.01) in comparison to the LR group. In addition, resuscitation with NS resulted in significantly lower fibrinogen levels (99 +/- 21 mg/dL versus 123 +/- 20 mg/dL, p = 0.02). The serum lactate was 4.7 +/- 2.2 in the LR group and 1.7 +/- 1.7 in the NS swine (p < 0.01) at the end of the study. CONCLUSIONS: Resuscitation of uncontrolled hemorrhagic shock with NS requires significantly greater volume and is associated with greater urine output, hyperchloremic acidosis, and dilutional coagulopathy as compared with LR. Resuscitation with LR results in an elevation of the lactate level that is not associated with acidosis. Lactated Ringer's solution is superior to NS for the resuscitation of uncontrolled hemorrhagic shock in swine.     

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.     

Changes in intracranial pressure, coagulation, and neurologic outcome after resuscitation from experimental traumatic brain injury with hetastarch

BACKGROUND: In a model of traumatic brain injury (TBI), 2 protocols compared changes in intracranial pressure (ICP), coagulation, and neurologic outcome after intravenous fluid (IVF) resuscitation with either Hextend (HEX, 6% hetastarch in lactated electrolyte injection) or standard of care, crystalloid plus mannitol (MAN). METHODS: In the nonsurvivor protocol, swine (n = 28) received a fluid percussion TBI and hemorrhage (27 +/- 3 mL/kg). At 30 minutes, resuscitation began with lactated Ringer's (LR) or HEX. After 60 minutes, MAN (1 g/kg) or placebo was given plus supplemental IVF to maintain cerebral perfusion pressure (CPP) > or = 70 mm Hg for 240 minutes. Swine in the survivor group (n = 15) also underwent TBI and hemorrhage, and resuscitation with HEX was compared to that of normal saline (NS)+MAN. Neurologic outcome and coagulation were evaluated for 72 hours. RESULTS: In the nonsurvivor protocol, HEX, LR+MAN, and HEX+MAN attenuated the time-related rise of ICP and prevented ICP >20 mm Hg versus LR alone (P < .05). HEX alone maintained CPP (relative to baseline) and decreased total IVF by 50% versus LR +/- MAN (P < .05). MAN had no additive effect with HEX. Coagulation, measured by thromboelastograph reaction time (R), was 11 +/- 1 and 9 +/- 1 minutes at baseline and after TBI (before randomization). At 240 minutes after HEX or LR+MAN, R was 6 +/- 1 or 7 +/- 2 minutes, which indicates a hypercoagulable state, but there was no difference between treatments. In the survivor protocol, ICP and CPP were similar with NS+MAN versus HEX, but IVF requirement was 161 +/- 20 versus 28 +/- 3 mL/kg (P < .05). Motor scores were higher on days 2 and 3 with HEX (P < .05). At 72 hours, R was 28 +/- 14 versus 26 +/- 6 minutes with NS+MAN versus HEX, which indicates a hypocoagulable state, but there was no difference between treatments. CONCLUSIONS: Hextend as the sole resuscitation fluid after severe TBI reduces fluid requirement, obviates the need for mannitol, improves neurologic outcome, and has no adverse effect on the coagulation profile relative to the crystalloid plus mannitol standard of care.     

Fluid resuscitation improves hemodynamics without increased bleeding in a model of uncontrolled hemorrhage induced by an iliac artery tear in dogs

BACKGROUND: Fluid resuscitation administered before hemorrhage control for trauma victims sustaining penetrating abdominal injury is controversial. Our objective was to evaluate intra-abdominal blood loss and hemodynamic and metabolic effects of no fluid resuscitation, small-volume 7.5% sodium chloride/6% dextran-70 (HSD), or large-volume lactated Ringer's (LR) solution during intra-abdominal vascular injury and uncontrolled hemorrhage. METHODS: In pentobarbital-anesthetized dogs (n = 26, 17 +/- 0.3 kg), a suture was placed through the common iliac artery to produce a 3-mm tear when the exteriorized suture lines were pulled after incision closure. Dogs were randomized to three groups, according to the treatment used after 20 minutes of uncontrolled hemorrhage: controls, no fluid resuscitation (CT group) (n = 6); the HSD group (4 mL/kg over 4 minutes, n = 6); and the LR group (32 mL/kg over 15 minutes, n = 6). After 40 minutes of uncontrolled bleeding, animals were killed, and intra-abdominal blood loss was measured. RESULTS: Eight dogs died from severe hemorrhagic shock before randomization and were excluded. After 20 minutes, animals presented lower blood pressure (approximately 35 mm Hg), low cardiac output (approximately 1.0 L/min/m(2)), and metabolic acidosis (pH approximately 7.23, base excess approximately -9 mmol/L). After HSD and LR solution, arterial pressure presented a transient increase, but remained below baseline. Two animals died before the end of the experiment, both in the LR group. Cardiac index was partially improved in the LR and HSD groups, whereas the CT group sustained a low-flow state. There were no significant differences between groups regarding intra-abdominal blood loss (CT group, 47.8 +/- 5.9 mL/kg; HSD group, 41.7 +/- 2.3 mL/kg; and LR group, 49.4 +/- 0.7 mL/kg). CONCLUSION: Fluid resuscitation with either large-volume LR solution or small-volume HSD, during uncontrolled hemorrhage from intra-abdominal vascular injury, produced hemodynamic and metabolic benefits, without additional blood loss, whereas no fluid resuscitation was associated with sustained low cardiac output and hypotension.     

Resuscitation with a novel hemoglobin-based oxygen carrier in a Swine model of uncontrolled perioperative hemorrhage

BACKGROUND: Systemic and pulmonary hypertension, possibly related to nitric oxide scavenging by free hemoglobin (Hb), is often seen during resuscitation with hemoglobin-based oxygen carriers (HBOCs). Recently, a second-generation HBOC, rHb2.0 for Injection (rHb), has been developed using recombinant human Hb that has reduced reactivity with nitric oxide. The current study evaluates the efficacy of this novel compound for resuscitation in a swine model of uncontrolled perioperative hemorrhage. METHODS: After instrumentation, animals underwent splenectomy and rapid hemorrhage to a systolic blood pressure of 35 mm Hg and isoelectric electroencephalography. 15 minutes of shock was followed by resuscitation over 30 minutes. In phase I, 18 animals were randomized into three resuscitation groups: (1) lactated Ringer's (LR) equal to three times the shed blood, the negative control group; (2) heterologous blood (BL) equal to Hb 2 g/kg, the positive control group; and (3) rHb equal to 2 g/kg, the treatment group. In phase II, six animals underwent the same experiment with a first-generation HBOC, diaspirin cross-linked Hb (DCLHb) equal to 2 g/kg, an additional control group. On day 0 after 2 hours of observation, spontaneously breathing animals were returned to their cages. Surviving animals were redosed on days 1, 2, and 3 (rHb/DCLHb 1 g/kg; LR/BL-LR 500 mL). Survivors were killed on day 5 and organs harvested for histologic examination. Group comparisons were performed using Student's t test, repeated-measures analysis of variance, and chi2 test. Significance was set at 95% confidence intervals. RESULTS: After resuscitation, systemic mean arterial pressure (MAP) (baseline = 107 +/- 15 mm Hg) was 128 +/- 34 and 108 +/- 15 mm Hg in rHb and BL animals, respectively, and remained stable. In LR and DCLHb animals, after normalization, MAP declined to 67 +/- 13 and 84 +/- 34 mm Hg, respectively. The rHb group maintained higher MAP than the LR and BL groups (p < 0.05 vs. both). With resuscitation, mean pulmonary arterial pressure (PAP) (baseline = 25 +/- 5 mm Hg) increased in rHb (40 +/- 4 mm Hg), BL (34 +/- 3 mm Hg), and DCLHb (40 +/- 3 mm Hg) groups, but stayed elevated only in the DCLHb group (36 +/- 3 mm Hg). PAP in the rHb group was similar to the BL group (p > 0.05), and both rHb and BL groups showed a higher PAP than the LR group (p < 0.05 vs. both). PAP was highest in the DCLHb group (p < 0.05 vs. rHb). Cardiac output of rHb and BL groups was similar (p > 0.05) throughout the observation period. Arterial lactate increased to 5.6 +/- 2.5 mmol/L with shock and then normalized to < 2.0 mmol/L in the rHb, BL, and LR groups within 30 minutes of resuscitation. It remained elevated to > 3.5 mmol/L and showed a delayed increase in the DCLHb group (p < 0.05). Causes and number of deaths were as follows: rHb, zero of six; BL-transfusion reaction, one of six; LR-irreversible shock, four of six; and DCLHb-ventricular failure, six of six. There was no significant increase in plasma methemoglobin (rHb) and no difference in liver or cardiac enzymes (rHb vs. BL). No histologic abnormalities were seen in the rHb group except for cytoplasmic vacuolation, a process thought to be related to metabolism of the test article. CONCLUSION: rHb2.0 for Injection, a second-generation recombinant human HBOC, performs as well as heterologous blood for resuscitation after perioperative blood loss, does not cause sustained pulmonary hypertension, maintains adequate cardiac output and oxygen delivery, and is superior to either LR or DCLHb.     

A single bolus of 3% hypertonic saline with 6% dextran provides optimal initial resuscitation after uncontrolled hemorrhagic shock

BACKGROUND: The optimal fluid for early resuscitation of hemorrhagic shock would restore perfusion without increasing blood loss, hypothermia, acidosis, or coagulopathy. This study examined effects of a single bolus of hypertonic saline (HTS) with or without (+/-) dextran (D) after uncontrolled hemorrhage (UH) and determined optimal fluid composition. METHODS: Fifty swine were anesthetized and underwent invasive line placement, celiotomy, splenectomy, suprapubic catheterization, and grade V liver injury. After 30 minutes of UH, blinded fluid resuscitation was initiated with a 250-mL bolus. Animals were randomized to five groups: normal saline (NS), 3% HTS (3%), 3% HTS/6% D (3% D), 7.5% HTS (7.5%), or 7.5% HTS/6% D (7.5% D). Mean arterial pressure (MAP) and tissue oxygen saturation (StO2) were recorded. Laboratory and thrombelastography (TEG) data were collected every 30 minutes. Animals were sacrificed 120 minutes after injury. Analysis of variance was used to compare groups. Significance was defined as p < 0.05. RESULTS: Baseline characteristics and laboratory values were similar in all groups. All groups achieved a similar degree of shock. Two NS and two 3% animals did not survive to 120 minutes. Fluids containing dextran produced a significantly greater increase in MAP (p < 0.02). Animals receiving 3% D maintained a higher MAP 90 minutes after fluid bolus. Also, 7.5% +/- D produced a significantly greater initial increase in StO2 (p < 0.05). This effect declined after fluid bolus while 3% D continued to improve tissue oxygenation. Significant differences developed between groups in TEG values, hematocrit, fibrinogen, urine sodium, serum sodium, serum chloride, and urine output. CONCLUSIONS: A single bolus of 3% D after uncontrolled hemorrhagic shock produces an adequate and sustained rise in MAP and StO2 and attenuates hypercoagulability. Resuscitation with 7.5% +/- D produces significantly increased urine output accompanied by a decline in MAP and StO2 over time. A single bolus of 7.5% D results in significant dilutional anemia and relative hypofibrinogenemia.     

Tissue oxygen monitoring during hemorrhagic shock and resuscitation: a comparison of lactated Ringer's solution,hypertonic saline dextran,and HBOC-201

BACKGROUND: The ideal resuscitation fluid for the trauma patient would be readily available to prehospital personnel, universally compatible, effective when given in small volumes, and capable of reversing tissue hypoxia in critical organ beds. Recently developed hemoglobin-based oxygen-carrying solutions possess many of these properties, but their ability to restore tissue oxygen after hemorrhagic shock has not been established. We postulated that a small-volume resuscitation with HBOC-201 (Biopure) would be more effective than either lactated Ringer's (LR) solution or hypertonic saline dextran (HSD) in restoring baseline tissue oxygen tension levels in selected tissue beds after hemorrhagic shock. We further hypothesized that changes in tissue oxygen tension measurements in the deltoid muscle would reflect the changes seen in the liver and could thus be used as a monitor of splanchnic resuscitation. METHODS: This study was a prospective, blinded, randomized resuscitation protocol using anesthetized swine (n = 30), and was modeled to approximate an urban prehospital clinical time course. After instrumentation and splenectomy, polarographic tissue oxygen probes were placed into the liver (liver PO2) and deltoid muscle (muscle PO2) for continuous tissue oxygen monitoring. Swine were hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg over 20 minutes, shock was maintained for another 20 minutes, and then 100% oxygen was administered. Animals were then randomized to receive one of three solutions: LR (12 mL/kg), HSD (4 mL/kg), or HBOC-201 (6 mL/kg). Physiologic variables were monitored continuously during all phases of the experiment and for 2 hours postresuscitation. RESULTS: At a MAP of 40 mm Hg, tissue PO2 was 20 mm Hg or less in both the liver and muscle beds. There were no significant differences in measured liver or muscle PO2 values after resuscitation with any of the three solutions in this model of hemorrhagic shock. When comparing the hemodynamic effects of resuscitation, the cardiac output was increased from shock values in all three animal groups with resuscitation, but was significantly higher in the animals resuscitated with HSD. Similarly, MAP was increased by all solutions during resuscitation, but remained significantly below baseline except in the group of animals receiving HBOC-201 (p < 0.01). HBOC-201 was most effective in both restoring and sustaining MAP and systolic blood pressure. There was excellent correlation between liver and deltoid muscle tissue oxygen values (r = 0.8, p < 0.0001). CONCLUSION: HBOC-201 can be administered safely in small doses and compared favorably to resuscitation with HSD and LR solution in this prehospital model of hemorrhagic shock. HBOC-201 is significantly more effective than HSD and LR solution in restoring MAP and systolic blood pressure to normal values. Deltoid muscle PO2 reflects liver PO2 and thus may serve as an index of the adequacy of resuscitation in critical tissue beds.     

Hypotensive resuscitation using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) leads to reversal of anaerobic metabolism.

BACKGROUND: Traditional resuscitation regimens have been recently challenged. This study evaluates hypotensive resuscitation with a hemoglobin-based oxygen-carrying (HBOC) solution after severe hemorrhage in a porcine model. We hypothesized that HBOC-201 restores tissue perfusion at a lower mean arterial pressure than standard resuscitation fluids. METHODS: Yorkshire swine (55-65 kg, n = 30), were rapidly hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, maintained hypotensive for 45 minutes, and randomized into groups. Group I was resuscitated with an HBOC solution to a MAP of 60 mm Hg. Groups II and III were resuscitated to a MAP of 80 mm Hg with lactated Ringer's solution (LR) alone or LR (40 mL/kg) followed by shed blood, respectively. Group IV was resuscitated with shed blood alone to a MAP of 60 mm Hg. Group V received an HBOC solution to a MAP of 50 mm Hg. Hemodynamic variables, Swan-Ganz parameters, blood gas samples, and lactate levels were followed for 5 hours. Data were analyzed by analysis of variance/Duncan multiple range test. RESULTS: There were no significant differences in mortality between any groups. Groups I, IV, and V had lower (p < 0.05) cardiac output, pulmonary artery wedge pressure, and MAP than either group II or group III. Svo2 was significantly lower in the HBOC groups. There were no significant differences in arterial pH or lactate between groups I, III, and IV. Lactate levels, base excess, and arterial pH were significantly worse in the LR-alone and HBOC-50 groups. CONCLUSION: Hypotensive resuscitation with HBOC-201 at a MAP of 60 mm Hg after a controlled hemorrhage in swine provides sufficient tissue perfusion and oxygen delivery to reverse anaerobic metabolism on the basis of global physiologic markers despite continued hypotension, hypovolemia, and low cardiac output.     

A double-blind study of the effect on hemostasis of nabumetone (Relafen) compared to placebo.

A double-blind, placebo-controlled clinical trial comparing the effect on hemostasis of nabumetone (Relafen) to placebo in patients who were about to undergo forefoot surgery was performed. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are reported to inhibit platelet cyclooxygenase activity, resulting in altered platelet function and thus potentially enhanced bleeding. Nabumetone has been reported to have no effect on platelet aggregation and bleeding time in normal volunteers and in patients who have undergone knee arthroscopy. After fulfilling the inclusion criteria and after a 1-week washout period (acetaminophen controlled), 15 patients were enrolled in the nabumetone group and 15 patients were randomized in the placebo group. Hemostatic parameters [prothrombin time (PT), partial thromboplastin time (PTT), and Ivy bleeding time (IBT)] were assessed at baseline, visit 2, visit 3, and final visit. No meaningful differences were observed between treatment groups in any of the measured hemostatic parameters. No significant adverse events were reported. There was no significant change from baseline for PT, PTT, and IBT in the nabumetone group (PT, p < .06; PTT, p < .64; IBT, p < .17) versus the placebo group (PT, p < .61; PTT, p < .63; IBT, p < .25). The lack of bleeding diathesis and significant prolongation of PT, PTT, or IBT in this study suggests that nabumetone in dosages up to 1000 mg/day can be administered safely in the immediate preoperative period to patients undergoing forefoot surgery.     

Blood loss after fluid resuscitation with isotonic or hypertonic saline for the initial treatment of uncontrolled hemorrhage induced by spleen rupture

BACKGROUND: It has been suggested that fluid resuscitation for the prehospital management of hypotensive trauma victims increases bleeding. In a model of uncontrolled hemorrhage induced by complete splenic laceration with a hilar vascular injury, we hypothesized that small-volume hypertonic saline or large-volume lactated Ringer's solution may provide sustained hemodynamic benefits despite promoting increases in intra-abdominal bleeding. METHODS: Forty anesthetized, spontaneously breathing dogs (18 +/- 1 kg) underwent laparotomy. A suture line was placed around the spleen to produce a splenic rupture with hilar vascular injury by pulling the exteriorized lines after incision closure. Intra-abdominal blood loss was measured directly, immediately after the animal was killed. Dogs were randomly assigned to four groups (n = 10 per group): Untreated controls were killed 20 (CT20) or 40 (CT40) minutes after splenic rupture to measure blood loss directly. Treatment groups received (20 minutes after spleen rupture) lactated Ringer's (LR), 33 mL/kg over 15 minutes, or 7.5% NaCl/6% dextran 70 (HSD), 4 mL/kg over 4 minutes. Blood loss was measured 40 minutes after spleen rupture. RESULTS: Mean arterial pressure dropped from an average value of 103 +/- 3 mm Hg to 67 +/- 5 mm Hg during the first 20 minutes and was partially restored afterward in all groups, with no significant differences between them. No resuscitation was associated with low cardiac output, whereas HSD restored and LR overshot baseline cardiac output. Intra-abdominal blood loss was 30 +/- 4, 38 +/- 4, 43 +/- 5, and 42 +/- 5 mL/kg for groups CT20, CT40, HSD, and LR, respectively, with no statistical significance between groups. CONCLUSION: No-fluid resuscitation in uncontrolled hemorrhage from splenic rupture resulted in a low-flow state, whereas resuscitation with small volumes of HSD or large volumes of LR produced hemodynamic benefits without significant increases in bleeding.     

Does bicarbonate correct coagulation function impaired by acidosis in swine?

BACKGROUND: Coagulopathy is an important contributor to morbidity and mortality in trauma patients. Acidosis contributes to coagulopathy. Acidosis can be neutralized with intravascular bicarbonate, but it is unclear if the coagulation defect is rapidly reversed. The effects of acidosis and bicarbonate neutralization on coagulation function were investigated in vivo. METHODS: Acidosis was induced in 12 pigs by infusing 0.2 mol/L HCl to pH 7.1. Pigs were then infused with either LR to maintain a pH of 7.1 (A-LR, n = 6) or 0.3 mol/L bicarbonate to a pH of 7.4 (A-Bi, n = 6). Blood samples were taken at baseline, 15 minutes after acidosis induction, and 15 minutes after bicarbonate neutralization. Coagulation function was assessed by prothrombin time (PT), partial thromboplastin time (PTT), thrombin generation, initial clot formation time (R), clotting rapidity (alpha), and clot strength (MA). RESULTS: Compared with baseline values, acidosis reduced fibrinogen concentration to 66% +/- 2% in A-LR and to 71% +/- 3% in A-Bi, and decreased platelet counts to 49% +/- 4% in A-LR and to 53% +/- 4% in A-Bi. Thrombin generation decreased to 60% +/- 4% in A-LR and to 53% +/- 7% in A-Bi. Acidosis prolonged PT and PTT about 20% and decreased alpha and MA. After pH neutralization, fibrinogen and platelet levels remained depleted and no reversal of acidosis-induced changes in thrombin generation, PT, PTT, alpha, and MA were observed. CONCLUSION: Acidosis impaired coagulation by depleting fibrinogen and platelets and by inhibiting clotting kinetics. The deficit associated with acidosis was not reversed with bicarbonate pH neutralization.     

Thromboelastography Use in the Acute Young Trauma Patient: Early Experience of Two Level One Trauma Centers

BackgroundThromboelastography (TEG) point-of-care systems allow for analysis of the sum of platelet function, coagulation proteases and inhibitors, and the fibrinolytic system within 30 minutes. This allows a clinician to guide transfusion more precisely with an appropriate type of blood product. Literature has supported that TEG-guided resuscitation had lower mortality compared to standardized 1:1:1 (red blood cells (RBC), fresh-frozen plasma (FFP), and platelets) massive transfusion protocol (MTP) in penetrating trauma patients, but data has been sparse in examining the young trauma patient.MethodsThis was a cross-sectional chart review study performed with patients up to 30 years old seen in two level one trauma centers serving children with active bleeding resulting from trauma from January 1, 2010 to June 26, 2018. TEG use was evaluated in these patients.Results258 patients were included in the analysis. 112 (43%) had penetrating trauma and 225 (87%) had polytrauma. MTP was instituted in 176 (69%) patients and 88 (34%) patients who had TEG measured. There were significant correlations between PTT and alpha (r=-0.46; p<0.001), PTT and Kinetics (r=0.53; p<0.001), PTT and maximum amplitude (r=0.449; p<0.001). There were also significant correlations between PT and alpha (r=-0.29; p=0.008), and PT and maximum amplitude (r= -0.27; p=0.013). There was no significant correlation between TEG measures and INR. There were significant associations with requiring surgery within 24 hours 45% vs 61% (p=0.018), receiving TXA 20% vs 59% (p<0.001), and with receiving MTP 62% vs 83% (p=0.001), respectively.ConclusionsMeasurement of TEG was associated with patients receiving TXA, MTP and larger amounts of blood products. Components of TEG correlated with PT and PTT levels. Although there was no association with survival to hospital discharge, patients having TEG measured were more likely to undergo surgery within the first 24 hours of hospital arrival.     

Early vasopressin improves short-term survival after pulmonary contusion

Arginine vasopressin (AVP) is a promising treatment for several types of irreversible shock, but its therapeutic potential has not been examined after severe chest trauma. Two series of experiments were performed to fill this gap. METHODS: Series 1: anesthetized, mechanically-ventilated pigs (n = 20, 29 +/- 1 kg) received a blast to the chest, followed by a "controlled" arterial hemorrhage to a mean arterial pressure (MAP) <30 mm Hg. At 20 minutes, a 10 mL/kg normal saline (NS) bolus was followed by either 0.1 U/kg AVP bolus or NS, in randomized, blinded fashion. From 30-300 minutes, either AVP (0.4 U/kg/hr plus NS) or NS alone was infused as needed to MAP>70 mm Hg. Series 2: Swine (n = 15) received the chest injury followed by partial left hepatectomy to produce "uncontrolled" hemorrhage. Resuscitation was the same as in series 1. RESULTS: The blast created bilateral parenchymal contusions (R > L), hemo/pneumothorax and progressive cardiopulmonary distress. In Series 1, there were 3/20 deaths before randomization, 0/8 deaths after resuscitation with AVP versus 4/9 deaths with NS (p = 0.029). In surviving animals, with AVP versus NS, fluid requirements and peak airway pressures were lower while P/F was higher (all p < 0.05). In Series 2, with uncontrolled hemorrhage, there were 5/15 deaths before randomization. Upon resuscitation with AVP versus NS, survival time and blood loss were both improved, but the differences did not reach statistical significance. CONCLUSIONS: After severe chest trauma with controlled hemorrhage, early AVP decreased mortality, reduced fluid requirements and improved pulmonary function. With uncontrolled hemorrhage, early AVP did not increase the risk for bleeding.     

Effect of initially limited resuscitation in a combined model of fluid-percussion brain injury and severe uncontrolled hemorrhagic shock

OBJECT: Studies of isolated uncontrolled hemorrhage have indicated that initial limited resuscitation improves survival. Limited resuscitation has not been studied in combined traumatic brain injury and uncontrolled hemorrhage. In this study the authors evaluated the effects of limited resuscitation on outcome in combined fluid-percussion injury (FPI) and uncontrolled hemorrhage. METHODS: Twenty-four swine weighing 17 to 24 kg each underwent FPI (3 atm) and hemorrhage to a mean arterial pressure (MAP) of 30 mm Hg in the presence of a 4-mm aortic tear. Group I (nine animals) was initially resuscitated to a goal MAP of 60 mm Hg; Group II (nine animals) was resuscitated to a goal MAP of 80 mm Hg; and Group III (control; six animals) was not resuscitated. After 60 minutes, the aortic hemorrhage was controlled and the animals were resuscitated to baseline physiological parameters and observed for 150 minutes. Mortality rates were 11%, 50%, and 100% for Groups I, II, and III, respectively (Fisher's exact test; p = 0.002). The total hemorrhage volume was greater in Group II (69+/-32 ml/kg), as compared with Group I (41+/-18 ml/kg) and Group III (37+/-3 ml/kg) according to analysis of variance (p < 0.05). In surviving animals, cerebral perfusion pressure, cerebral blood flow (CBF), cerebral venous O2 saturation (ScvO2), and cerebral metabolic rate of O2 did not differ among groups. Although CBF was approximately 50% of baseline during the period of limited resuscitation in Group I, ScvO2 remained greater than 60%, and arteriovenous O2 differences remained within normal limits. CONCLUSIONS: In this model of FPI and uncontrolled hemorrhage, early aggressive resuscitation, which is currently recommended, resulted in increased hemorrhage and failure to optimize cerebrovascular parameters. In addition, a 60-minute period of moderate hypotension (MAP = 60 mm Hg) was well tolerated and did not compromise cerebrovascular hemodynamics, as evidenced by physiological parameters that remained within the limits of cerebral autoregulation.     

Changes in the hemostatic system after laparoscopic cholecystectomy

A 30 degrees reverse Trendelenburg position and the pneumoperitoneum performed in patients undergoing at Laparoscopic Cholecystectomy (LC) cause haemodynamic modifications in inferior cava vein and in femoral veins producing a venous stasis in lower limbs. So that activation of coagulation with hypercoagulability occurs. The aim of this study is to value the modification of the haemocoagulative and fibrinolytic factors during LC and OC. 18 patients with symptomatic and non complicated lithiasis were examined. They were divided in two groups, nine patients for each group. LC was performed in first group and OC in the other group. Prothrombin time (PT), plasma-activated partial thromboplastin time (PTT), Antithrombin III (AT III) fibrinogen degradation products (FDP) were valued before and at 6, 12, 24, 48 hours after operation. For the statistical analysis Student "t" for average comparison was used. There were no relevant alterations of PT, PTT and ATIII after operation in the two groups. FP was increased after surgery, especially at 24th-48th hours in the group in which OC (p < 0.05) was performed. FDP were increased in both groups but only at 24 and 48 hour after OC (p < 0.05) the result was significant. Earlier mobilization and reduced invasivity of laparoscopy could contrast thrombotic effects of the blood stasis in the lower limbs when 30 degrees-45 degrees reverse Trendelenburg and pneumoperitoneum are performed.     

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目的　探讨限制性液体复苏对出血未控制性休克后续救治的影响。方法　应用脾组织和血管损伤制作重度未控制出血性休克模型 ,比较早期限制液体复苏 [平均动脉压 (MAP)分别维持在 4 0mmHg(NS4 0组 ,1mmHg =0 .133kPa)、5 0mmHg(NS5 0组 )和 6 0mmHg(NS6 0组 ) ]和大量液体复苏 [MAP分别维持在 80mmHg(NS80组 )和 10 0mmHg(NS10 0组 ) ]对MAP、血乳酸 (BL)、红细胞压积 (HCT)、出血量、输液量及存活率的影响。结果　NS4 0、NS5 0和NS6 0组的出血量、液体用量和存活率明显低于NS80和NS10 0组 (P均 <0 .0 5 ) ;伤后4 5min ,NS80和NS10 0组HCT明显低于NS4 0、NS5 0和NS6 0组 (P均 <0 .0 5 ) ;伤后 4 0 5min ,NS80和NS10 0组的HCT明显低于NS5 0和NS6 0组 ,MAP明显低于NS4 0、NS5 0和NS6 0组 ,血乳酸明显高于NS4 0、NS5 0和NS6 0组 (P均 <0 .0 5 )。结论　在出血未控制条件下 ,早期限制性液体复苏可明显降低出血量 ,减轻酸中毒 ,为后续救治创造条件 ,并有利于最终存活率的提高     

Low-volume resuscitation with a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhage

BACKGROUND: We have shown in a previous work that HBOC-201 is able to reverse anaerobic metabolism at low volumes in a porcine model of controlled hemorrhage. On the basis of these results, we hypothesize that low-volume resuscitation with HBOC-201 in a porcine model of controlled hemorrhage provides adequate tissue oxygenation to limit end-organ damage and allow for survival of the animal. METHODS: Twenty-four Yorkshire swine (55-65 kg) were rapidly hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, maintained hypotensive for 45 minutes, and then divided into four groups. The first group, Shed Blood (BL), was resuscitated with shed blood to baseline MAP. A second group, Shed Blood (60), underwent resuscitation for four hours at an MAP of 60 mm Hg with shed blood. The third group, LR + Blood, was resuscitated with lactated Ringer's (maximum, 40 mL/kg) followed by shed blood to baseline MAP. The final group, HBOC (60), underwent resuscitation for 4 hours at an MAP of 60 mm Hg with HBOC-201. Hemodynamic variables, urine output, blood gas analyses, lactate levels, and jejunal oximetry were followed throughout the experiment. Animals were allowed to survive and underwent necropsy on postinjury day 3. Histologic comparisons were made. Data were analyzed using analysis of variance/Duncan's multiple range test. RESULTS: All animals survived the hemorrhage/resuscitation. One animal in the LR + Blood group died on postinjury day 1. Heart rate, MAP, and arterial pH were similar between groups. Cardiac output was significantly lower throughout resuscitation in the HBOC (60) group. Jejunal oximetry was similar throughout the experiment in all groups, revealing a decline in Po2 during hemorrhage and return to baseline or near baseline during resuscitation. There was no evidence of renal dysfunction. Histologically, one animal in the LR + Blood group and four of six animals in the HBOC (60) group demonstrated mild hepatocellular damage. All other tissues examined were found to have no significant abnormalities. Elevations in serum aspartate aminotransferase levels were noted when comparing the HBOC (60) group to the Shed Blood (BL) and Shed Blood (60) groups on day 2. Significant decreases in hemoglobin levels were noted in the HBOC (60) group compared with all other groups beginning on day 2. CONCLUSION: Low-volume resuscitation with HBOC-201 provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhagic shock with no long-term organ dysfunction identified. Although some animals did show mild hepatocellular damage with elevations of aspartate aminotransferase at day 2, these findings did not appear to have clinical relevance, and the enzyme elevations were trending toward normal by the third postoperative day. Decreases in hemoglobin levels at the later time points were expected, given the half-life of the product.     

Comparative analysis of hemostatic agents in a swine model of lethal groin injury

BACKGROUND: Techniques for better hemorrhage control after injury could change outcome. A large-animal model of lethal, uncontrolled hemorrhage was developed to test whether the use of various hemostatic agents would decrease bleeding and improve early survival. METHODS: A complex groin injury was created in 30 Yorkshire swine (42-55 kg) to produce uncontrolled hemorrhage. This injury included semitransection of the proximal thigh and complete division of the femoral artery and vein. After 5 minutes, the animals were randomized to (n = 6 animals per group) no dressing (ND), standard dressing (SD), SD and Rapid Deployment Hemostat (RDH) bandage, SD and QuikClot hemostatic agent (QC), or SD and TraumaDEX (TDEX). Limited volume 0.9% saline (1,000 mL over 30 minutes) resuscitation was started 30 minutes after injury. We measured blood loss, early mortality (180 minutes), and physiologic markers of hemorrhagic shock (e.g., cardiac output, blood pressure, hemoglobin, metabolic acidosis). RESULTS: Application of wound dressing decreased mortality in all groups compared with the ND group (83% mortality). However, this difference was significant (p < 0.05) only for the QuikClot hemostatic agent (0% mortality). Before the application of dressing (first 5 minutes), there were no differences in blood loss between the groups. After application of dressings, the QC group had the lowest blood loss (4.4 +/- 1.4 mL/kg). CONCLUSION: Of the hemostatic agents tested, QuikClot improved survival and decreased bleeding in a swine model of lethal vascular and soft tissue injury.