Hypotensive Fluid Resuscitation Research Articles

Effectiveness and safety of hypotension fluid resuscitation in traumatic hemorrhagic shock: A systematic review and meta-analysis of randomized controlled trials.

BackgroundAlthough the resuscitation of an adult trauma patient has been researched and written about for the past century, the ideal fluid strategy to infuse during the initial resuscitation period remains unresolved. This work was aimed at assessing the effect of hypotensive versus conventional resuscitation strategies in traumatic hemorrhagic shock patients on mortality, and the need for blood transfusions including adverse events.MethodsThis systematic review and meta-analysis were performed following the PRISMA guidelines. Electronic databases were searched for randomized controlled trials (RCT) comparing the effect of hypotension versus conventional fluid resuscitation for traumatic hemorrhagic shock patients. Two reviewers independently performed the screening, data extraction, and bias assessment. The data analysis was completed using the Cochrane Collaboration’s software RevMan 5.4.ResultsData from 28 RCTs on 4503 patients were included in the final meta-analysis. Patients receiving hypotension fluid resuscitation compared with conventional fluid resuscitation experienced less mortality (12.5% vs. 21.4%; RR = 0.58; 95% CI: 0.51–0.66; p < 0.001), fewer adverse events (10.8% vs. 13.4%; RR = 0.70; 95% CI: 0.59–0.83; p < 0.001), including fever acute respiratory distress syndrome (7.8% vs. 16.8%) or multiple organ dysfunction syndrome (8.6% vs. 21.6%).ConclusionsThis meta-analysis showed that hypotensive fluid resuscitation significantly reduced the mortality of hypovolemic shock patients. Findings are low in certainty and should be interpreted with caution. Therefore, there is an urgent need for larger, multicenter, randomized trials to confirm these findings.

Resuscitation strategies with different arterial pressure targets after surgical management of traumatic shock.

IntroductionHypotensive fluid resuscitation has a better effect before and during surgical intervention for multiple trauma patients with haemorrhagic shock. However, it is questionable whether hypotensive fluid resuscitation is suitable after surgical intervention for these patients, and whether resuscitation with different mean arterial pressure (MAP) targets after surgical intervention can obtain different results. The aim of this study was to investigate these questions and to explore the underlying mechanisms.MethodsA total of 30 anesthetized piglets were randomly divided into 3 groups (n = 10 per group): low MAP, middle MAP, and high MAP, which had MAP targets of 60, 80, and 100 mmHg, respectively. All animals underwent femur fracture, intestine and liver injury, haemorrhagic shock, early hypotensive resuscitation, and surgical intervention. Then, the animals received fluid resuscitation with different MAP targets as mentioned above for 24 hours. Hemodynamic parameters and vital organ functions were evaluated.ResultsFluid resuscitation in the 80 mmHg MAP group maintained haemodynamic stability, tissue perfusion, and organ function better than that in the other groups. The 60 mmHg MAP group presented with profound metabolic acidosis and organ histopathologic damage. In addition, animals in the 100 mmHg MAP group exhibited severe tissue oedema, organ function failure, and histopathologic damage.ConclusionsIn our porcine model of resuscitation, targeting high MAP by fluid administration alone resulted in a huge increase in the infusion volume, severe tissue oedema, and organ dysfunction. Meanwhile, targeting low MAP resulted in persistent tissue hypoperfusion and metabolic stress. Hence, a resuscitation strategy of targeting appropriate MAP might be compatible with maintaining haemodynamic stability, tissue perfusion, and organ function.

Small-Volume 7.5% NaCl Adenosine, Lidocaine, and Mg2+ Has Multiple Benefits During Hypotensive and Blood Resuscitation in the Pig Following Severe Blood Loss

Currently, there is no effective small-volume fluid for traumatic hemorrhagic shock. Our objective was to translate small-volume 7.5% NaCl adenosine, lidocaine, and Mg hypotensive fluid resuscitation from the rat to the pig. Pigs (35-40 kg) were anesthetized and bled to mean arterial pressure of 35-40 mm Hg for 90 minutes, followed by 60 minutes of hypotensive resuscitation and infusion of shed blood. Data were collected continuously. University hospital laboratory. Female farm-bred pigs. Pigs were randomly assigned to a single IV bolus of 4 mL/kg 7.5% NaCl + adenosine, lidocaine and Mg (n = 8) or 4 mL/kg 7.5% NaCl (n = 8) at hypotensive resuscitation and 0.9% NaCl ± adenosine and lidocaine at infusion of shed blood. At 60 minutes of hypotensive resuscitation, treatment with 7.5% NaCl + adenosine, lidocaine, and Mg generated significantly higher mean arterial pressure (48 mm Hg [95% CI, 44-52] vs 33 mm Hg [95% CI, 30-36], p < 0.0001), cardiac index (76 mL/min/kg [95% CI, 63-91] vs 47 mL/min/kg [95% CI, 39-57], p = 0.002), and oxygen delivery (7.6 mL O2/min/kg [95% CI, 6.4-9.0] vs 5.2 mL O2/min/kg [95% CI, 4.4-6.2], p = 0.003) when compared with controls. Pigs that received adenosine, lidocaine, and Mg/adenosine and lidocaine also had significantly lower blood lactate (7.1 mM [95% CI, 5.7-8.9] vs 11.3 mM [95% CI, 9.0-14.1], p = 0.004), core body temperature (39.3°C [95% CI, 39.0-39.5] vs 39.7°C [95% CI, 39.4-39.9]), and higher base excess (-5.9 mEq/L [95% CI, -8.0 to -3.8] vs -11.2 mEq/L [95% CI, -13.4 to -9.1]). One control died from cardiovascular collapse. Higher cardiac index in the adenosine, lidocaine, and Mg/adenosine and lidocaine group was due to a two-fold increase in stroke volume. Left ventricular systolic ejection times were significantly higher and inversely related to heart rate in the adenosine, lidocaine, and Mg/adenosine and lidocaine group. Thirty minutes after blood return, whole-body oxygen consumption decreased in pigs that received adenosine, lidocaine, and Mg/adenosine and lidocaine (5.7 mL O2/min/kg [95% CI, 4.7-6.8] to 4.9 mL O2/min/kg [95% CI, 4.2-5.8]), whereas it increased in controls (4.2 mL O2/min/kg [95% CI, 3.5-5.0] to 5.8 mL O2/min/kg [95% CI, 4.9-5.8], p = 0.02). After 180 minutes, pigs in the adenosine, lidocaine, and Mg/adenosine and lidocaine group had three-fold higher urinary output (2.1 mL//kg/hr [95% CI, 1.2-3.8] vs 0.7 mL//kg/hr [95% CI, 0.4-1.2], p = 0.001) and lower plasma creatinine levels. Small-volume resuscitation with 7.5% NaCl + adenosine, lidocaine, and Mg/adenosine and lidocaine provided superior cardiovascular, acid-base, metabolic, and renal recoveries following severe hemorrhagic shock in the pig compared with 7.5% NaCl alone.

Is There a Place for Crystalloids and Colloids in Remote Damage Control Resuscitation?

Crystalloids and colloids are used in prehospital fluid resuscitation to replace blood loss and preserve tissue perfusion until definite surgical control of bleeding can be achieved. However, large volumes of fluids will increase bleeding by elevating blood pressure, dislodging blood clots, and diluting coagulation factors and platelets. Hypotensive fluid resuscitation strategies are used to avoid worsening of uncontrolled bleeding. This is largely supported by animal studies. Most clinical evidence suggests that restricting fluid therapy is associated with improved outcome. Remote damage control resuscitation emphasizes the early use of blood products and restriction of other fluids to support coagulation and tissue oxygenation. Controversy regarding the optimal choice and composition of resuscitation fluids is ongoing. Compared with crystalloids, less colloid is needed for the same expansion of intravascular volume. On the other hand, colloids may cause coagulopathy not only related to dilution. The most important advantage of using colloids is logistical because less volume and weight are needed. In conclusion, prehospital fluid resuscitation is considered the standard of care, but there is little clinical evidence supporting the use of either crystalloids or colloids in remote damage control resuscitation. Alternative resuscitation fluids are needed.

Initial resuscitation with plasma and other blood components reduced bleeding compared to hetastarch in anesthetized swine with uncontrolled splenic hemorrhage

Damage control resuscitation recommends use of more plasma and less crystalloid as initial resuscitation in treating hemorrhage. The purpose of this study was to evaluate resuscitation with either blood components or conventional fluids on coagulation and blood loss. Isofluorane-anesthetized, instrumented pigs (eight per group) underwent controlled hemorrhage of 24 mL/kg, 20-minute shock period, splenic injury with 15-minute initial bleeding, and hypotensive fluid resuscitation. Lactated Ringer's (LR) was infused at 45 mL/kg while hetastarch (high-molecular-weight hydroxyethyl starch 6%, Hextend, Hospira, Inc., Lake Forest, IL) and blood component (fresh-frozen plasma [FFP], 1:1 FFP:[red blood cells] RBCs, 1:4 FFP : RBCs, and fresh whole blood [FWB]) were infused at 15 mL/kg. Postresuscitation blood loss (PRBL), hemodynamics, coagulation, hematocrit, and oxygen metabolism were measured postinjury for 5 hours. Resuscitation with any blood component reduced PRBL of 52% to 70% compared to Hextend, with FFP resulting in the lowest PRBL. PRBL with LR (11.5 ± 3.0 mL/kg) was not significantly different from Hextend (17.9 ± 2.5 mL/kg) or blood components (range, 5.5 ± 1.5 to 8.6 ± 2.6 mL/kg). The volume expansion effect of LR was transient. All fluids produced similar changes in hemodynamics, oxygen delivery, and demand despite the oxygen-carrying capacity of RBC-containing fluids. Compared with other fluids, Hextend produced greater hemodilution and reduced coagulation measures, which could be caused by an indirect dilutional effect or a direct hypocoagulable effect. These data suggest that blood products as initial resuscitation fluids reduced PRBL from a noncompressible injury compared to Hextend, preserved coagulation, and provided sustained volume expansion. There were no differences on PRBL among RBCs-to-FFP, FWB, or FFP in this nonmassive transfusion model.

Effect of hypotensive fluid resuscitation on microcirculation in an uncontrolled hemorrhagic shock of pregnant rabbits

to study the effects of hypotensive resuscitation on microvascular perfusion in a clinically relevant model of uncontrolled hemorrhagic shock in pregnancy. thirty New Zealand white rabbits at 15 - 25 days, pregnanal age were randomly divided into three groups; Group normal saline traditional aggressive resuscitation (NS), traditional aggressive resuscitation in the prehospital phase with a large quantity of normal saline and Ringer's solution to maintain mean arterial pressure (MAP) at the approximately 80 mm Hg (1 mm Hg = 0.133 kPa) level: Group normal saline hypotensive resuscitation (NH) and group hypertonic hyperosmotic hypotension resuscitation (HHH), hypotensive resuscitation in the prehospital phase with a bolus dose of 4 ml/kg normal saline or hypertonic hydroxyl ethyl starch (10% hydroxyl ethyl starch +7.5% NaCl), followed by Ringer's solution to maintain MAP at 60 mm Hg. Production pregnant rabbit model with hemorrhagic shock. The experiment consisted of four phases:basic phase (0 miniutes), shock phase (0 - 30 miniutes), prehospital phase (30 - 90 miniutes) and hospital phase (90 - 180 miniutes). (1) arteriole and venule diameter were continuously monitored by microcirculatory detecting instrument; (2) functional capillary density (FCD) of each phase was expressed by the percentage of opening capillaries segments relative to basic phase; (3) blood pH, BE PCO(2), PO(2) in pregnant rabbits were determined with a Medica Easy Blood Gas Analyzer. (1) there were no significant differences among three groups in arteriole and venule diameter at baseline (P > 0.05). After hemorrhagic shock arteriole diameter were NS (50.8 ± 5.6) µm, NH (47.6 ± 3.7) µm, HHH (51.3 ± 2.4) µm, respectively, with no significant differences between groups (P > 0.05). At the end of prehospital resuscitation phase and hospital resuscitation phase, significant differences were found in arteriole diameter in group NS (52.8 ± 4.9, 56.0 ± 3.8) µm, NH (61.3 ± 2.9, 65.4 ± 3.2)µm and HHH group (67.0 ± 4.1, 74.1 ± 4.8) µm (P < 0.05); after hemorrhagic shock venule diameter were NS (79.6 ± 7.0) µm, NH (75.3 ± 5.3) µm and HHH (76.2 ± 5.8) µm, respectively, with no significant differences between groups (P > 0.05). At the end of prehospital resuscitation phase and hospital resuscitation phase, venule diameter were NS (81.1 ± 6.7, 84.4 ± 6.0) µm, NH (82.8 ± 3.3, 85.4 ± 4.3) µm and HHH (86.9 ± 5.8, 89.4 ± 6.8) µm, respectively, with no significant differences between groups (P > 0.05). (2) The values of FCD in every groups were all 100%. After hemorrhagic shock FCD were NS (39.8 ± 6.8)%, NH (43.9 ± 4.0)%, HHH (44.0 ± 4.8)%, respectively, with no significant differences between groups (P > 0.05); at the end of prehospital resuscitation phase and hospital resuscitation phase, FCD were NS (54.5 ± 7.3, 59.7 ± 4.8)%, NH (63.1 ± 5.8, 70.3 ± 5.6)% and HHH (80.5 ± 6.9, 91.7 ± 4.7)%, respectively, with significant differences between groups (P < 0.05). (3) Blood gas parameter: the values of blood pH, BE, PO(2), PCO(2) in pregnant rabbits in all groups were within normal bounds at basic phase. Shock phase induced typical hyperventilation in all groups, with increase of arterial PO(2) and decrease of PCO(2); at the end of hospital resuscitation phase, there were no significant difference among the three groups in the values of blood PCO(2) (P > 0.05); the values of blood PO(2) at the hospital resuscitation phase were significantly lower in NS groups than corresponding values in the other groups (P < 0.05). After hemorrhagic shock there was significant metabolic acidosis as shown by decrease of pH, BE; at prehospital resucitation phase, pH, BE values tended to increase in all the groups but not reach to base period. At the end of hospital resucitation phase. The pH, BE value was significantly higher in NS group than those in the other two groups (P < 0.05). (4) Median survival time in NS (2.1 ± 0.2) days group was significantly shorter than NH (3.0 ± 0.3) days and HHH (3.6 ± 0.3) days group (P < 0.05). FCD at the end of the hospital resuscitation were significantly related with survival time (r = 0.655, P = 0.000). compared with traditional aggressive fluid resuscitation, hypotensive resuscitation reduce constriction of arterial and venule diameter, increase FCD, alleviate metabolic acidosis and improve long-term survival. Hypertonic hydroxyl ethyl starch resuscitation ameliorate microcirculation without improving survival rate.

Preconditions of Hemostasis in Trauma: A Review. The Influence of Acidosis, Hypocalcemia, Anemia, and Hypothermia on Functional Hemostasis in Trauma

Beside the often discussed topics of consumption and dilution coagulopathy, additional perioperative impairments of coagulation are caused by acidosis, hypocalcemia, anemia, hypothermia, and combinations. Reviewing current literature, cutoff values of these parameters become obvious at which therapy should commence. A notable impairment of hemostasis arises at a pH < or = 7.1. Similar effects are caused by a BE of -12.5 or less. Thus, in case of severe bleeding, buffering toward physiologic pH values is recommended, especially with massive transfusions of older RBCCs displaying exhausted red blood cell buffer systems. It completes the optimization of the volume homeostasis to ensure an adequate tissue perfusion. Combining beneficial cardiovascular and coagulation effects, the level for ionized calcium concentration should be held > or = 0.9 mmol/L. From the hemostatic point of view, the optimal Hct is higher than the one required for oxygenation. Even without a "classical" transfusion trigger, the therapy of acute, persistent bleeding should aim at reaching an Hct > or = 30%. A core temperature of < or = 34 degrees C causes a decisive impairment of hemostasis. A controlled hypotensive fluid resuscitation should aim at reaching a mean arterial pressure of > or = 65 mm Hg (possibly higher for cerebral trauma). Prevention and later aggressive therapy of hypothermia by exclusive infusion of warmed fluids and the use of warming devices are prerequisites for the cure of traumatic coagulopathy. Combined appearance of single preconditions cause additive impairments of the coagulation system. The prevention and timely correction, especially of the combination acidosis plus hypothermia, is crucial for the treatment of hemorrhagic coagulopathy.

Titrated hypertonic/hyperoncotic solution for hypotensive fluid resuscitation during uncontrolled hemorrhagic shock in rats

Background: In volume- or pressure-controlled hemorrhagic shock (HS) a bolus intravenous infusion of hypertonic/hyperoncotic solution (HHS) proved beneficial compared to isotonic crystalloid solutions. During uncontrolled HS in animals, however, HHS by bolus increased blood pressure unpredictably, and increased blood loss and mortality. We hypothesized that a titrated i.v. infusion of HHS, compared to titrated lactated Ringer's solution (LR), for hypotensive fluid resuscitation during uncontrolled HS reduces fluid requirement, does not increase blood loss, and improves survival. Methods: We used our three-phased uncontrolled HS outcome model in rats. HS phase I began with blood withdrawal of 3 ml/100 g over 15 min, followed by tail amputation. Then, hydroxyethyl starch 10% in NaCl 7.2% was given i.v. to the HHS group ( n = 10) and LR to the control group ( n = 10), both titrated to prevent mean arterial pressure (MAP) from falling below 40 mmHg during HS time 20–90 min. At HS 90 min, resuscitation phase II of 180 min began with hemostasis, return of all the blood initially shed, plus fluids i.v. as needed to maintain normotension (MAP ≥ 70 mmHg). Liver dysoxia was monitored as increase in liver surface pCO 2 during phases I and II. Observation phase III was to 72 h. Results: During HS, preventing a decrease in MAP below 40 mmHg required HHS 4.9 ± 0.6 ml/kg (all data mean ± S.E.M.), compared to LR 62.2 ± 16.6 ml/kg ( P < 0.001), with no group difference in MAP. Uncontrolled blood loss during HS from the tail stump was 13.3 ± 1.9 ml/kg with HHS infusion, versus 12.6 ± 2.5 ml/kg with LR infusion ( P = 0.73). Serum sodium concentrations were moderately elevated at the end of HS in the HHS group (149 ± 3 mmol/l) versus the LR group (139 ± 1 mmol/l) ( P = 0.001), and remained elevated throughout. Liver pCO 2 increased during HS in both groups equally ( P < 0.001 versus baseline), and tended to return to baseline levels at the end of HS. Blood gas and lactate values throughout did not differ between groups. During HS, 2 of 10 rats in the HHS group versus 0 of 10 in the LR group died ( P = 0.47). There was no difference between HHS and LR groups in survival rates to 72 h (3 of 10 in the HHS group versus 2 of 10 in the LR group) ( P = 1.0). Survival times, by life table analysis, were not different ( P = 0.75). Conclusion: In prolonged uncontrolled HS, a titrated i.v. infusion of HHS can maintain controlled hypotension with only one-tenth of the volume of LR required, without increasing blood loss. This titrated HHS strategy may not increase the chance of long-term survival.

Prolonged severe hemorrhagic shock and resuscitation in rats does not cause subtle brain damage.

Some patients who survived severe hemorrhagic shock (HS) seem to exhibit persistent subtle neurobehavioral deficits. This finding is of concern if limited hypotensive fluid resuscitation is applied in hypotensive victims with penetrating trauma. This study was designed to determine whether subtle brain damage would occur in rats after severe prolonged HS. We hypothesized that rats surviving HS with mean arterial pressure (MAP) controlled at 40 mm Hg for 60 minutes would recover with slight permanent brain damage in terms of cognitive function without morphologic loss of neurons and that rats surviving HS with MAP at 30 mm Hg for 45 minutes (60 minutes were not tolerated) would have grossly abnormal brain function and loss of neurons. Under light nitrous oxide-halothane anesthesia, spontaneously breathing rats underwent MAP-controlled HS (HS phase I), volume resuscitation to normotension and invasive monitoring to 60 minutes (resuscitation phase II), and observation to 10 days with detailed assessment of cognitive function (observation phase III). Five conscious rats served as normal controls. Three treatment groups were compared: group 1, shams (11 of 12 rats survived to 10 days); group 2, HS at MAP 40 mm Hg for 60 minutes (10 of 17 rats survived); group 3, HS at 30 mm Hg for 45 minutes (10 of 14 rats survived). On post-HS day 10, all normal controls and all survivors of all three groups were functionally normal with overall performance category = 1 (normal) (overall performance category 1 = normal, 5 = death) and neurologic deficit scores < or = 7% (neurologic deficit scores 0-10% = normal, 100% = brain death). Post-HS beam balance, beam walking, and Morris water maze test results in HS groups 2 and 3 showed latencies not significantly different from those in shams and normal controls. Light microscopic scoring of five selectively vulnerable brain regions and other regions in five coronal sections revealed no ischemic (pyknotic, shrunken, eosinophilic) neurons in any of the survivors to 10 days. There was no statistical difference between normal controls, sham animals, and both HS groups in the number of normal neurons counted in the hippocampal CA-1 region in the 10-day survivors. All nonsurvivors died with intestinal necrosis. HS at MAP 40 mm Hg for 60 minutes or MAP 30 mm Hg for 45 minutes does not cause subtle functional or histologic brain damage in surviving rats. Controlling MAP at 30 mm Hg carries a risk of sudden cardiac arrest. These data suggest that limited fluid resuscitation, to maintain MAP at about 40 mm Hg, as recommended for victims of penetrating trauma with uncontrolled HS, is safe for the brain.

Resuscitation from severe hemorrhage

The potential to be successfully resuscitation from severe traumatic hemorrhagic shock is not only limited by the "golden 1 hr", but also by the "brass (or platinum) 10 mins" for combat casualties and civilian trauma victims with traumatic exsanguination. One research challenge is to determine how best to prevent cardiac arrest during severe hemorrhage, before control of bleeding is possible. Another research challenge is to determine the critical limits of, and optimal treatments for, protracted hemorrhagic hypotension, in order to prevent "delayed" multiple organ failure after hemostasis and all-out resuscitation. Animal research is shifting from the use of unrealistic, pressure-controlled, hemorrhagic shock models and partially realistic, volume-controlled hemorrhagic shock models to more realistic, uncontrolled hemorrhagic shock outcome models. Animal outcome models of combined trauma and shock are needed; a challenge is to find a humane and clinically realistic long-term method for analgesia that does not interfere with cardiovascular responses. Clinical potentials in need of research are shifting from normotensive to hypotensive (limited) fluid resuscitation with plasma substitutes. Topics include optimal temperature, fluid composition, analgesia, and pharmacotherapy. Hypotensive fluid resuscitation in uncontrolled hemorrhagic shock with the addition of moderate resuscitative (28 degrees to 32 degrees C) hypothermia looks promising in the laboratory. Regarding the composition of the resuscitation fluid, despite encouraging results with new preparations of stroma-free hemoglobin and hypertonic salt solutions with colloid, searches for the optimal combination of oxygen-carrying blood substitute, colloid, and electrolyte solution for limited fluid resuscitation with the smallest volume should continue. For titrating treatment of shock, blood lactate concentrations are of questionable value although metabolic acidemia seems helpful for prognostication. Development of devices for early noninvasive monitoring of multiple parameters in the field is indicated. Molecular research applies more to protracted hypovolemic shock followed by the systemic inflammatory response syndrome or septic shock, which were not the major topics of this discussion.