Crystalloid Volume Research Articles

Diluting the benefits of hemostatic resuscitation

Although minimization of crystalloids is a widely adopted practice in the resuscitation of patients with severe hemorrhage, its direct impact on high-ratio resuscitation (HRR) outcomes has not been analyzed. We hypothesize that HRR patients will have worse outcomes from crystalloid use. This was a 4-year retrospective multi-institutional analysis (MIA) of patients who received massive transfusion protocol (MTP) managed with damage-control laparotomy. Ratios of fresh frozen plasma-packed red blood cell (PRBC) were calculated and divided in two groups: HRR (1-1:2) and low-ratio resuscitation (LRR < 1:2). Major outcome of interest was to analyze the direct impact of 24-hour crystalloid volume on HRR MTP patients who received 10 or more units of PRBC. Statistical analysis included analysis of variance, Fisher's exact, Kaplan-Meier (KM) survival curves, and multiple logistic regression. Total of five Level I trauma centers participated with 451 patients who received MTP with 10 or more units of PRBC (fresh frozen plasma/PRBC ratios, n = 365 (80.9%) HRR vs. n = 86 (19.0%) LRR. Overall 24-hour KM survival for the HRR versus LRR was 85.2% versus 68.6% (p = 0.0004). The volume of crystalloids on KM survival curve in HRR MTP patients was not significant for mortality (p = 0.52). Morbidity odds ratios (95% confidence interval) for complications were not significant for HRR but were for crystalloids: bacteremia, 1.05 (1.0-1.1); adult respiratory distress syndrome, 1.13 (1.0-1.2), and acute renal failure, 1.05 (1.0-1.1). Our MIA results support previous studies with decreased mortality in HRR group when compared with LRR. This is the first MIA to demonstrate increased morbidity from crystalloid use in HRR. Within all MTPs with 10 or more units of PRBC, HRR was not a predictor of morbidity, but crystalloid volume was. Caution in overzealous use of crystalloid during HRR is warranted. Therapeutic study, level IV.

Initial assessment on the impact of crystalloids versus colloids during damage control resuscitation

BackgroundHigh ratios of fresh frozen plasma:packed red blood cells in damage control resuscitation (DCR) are associated with increased survival. The impact of volume and type of resuscitative fluid used during high ratio transfusion has not been analyzed. We hypothesize a difference in outcomes based on the type and quantity of resuscitative fluid used in patients that received high ratio DCR. MethodsA matched case control study of patients who received transfusions of ≥ four units of PRBC during damage control surgery over 4 1/2 y, was conducted at a Level I Trauma Center. All patients received a high ratio DCR, >1:2 of fresh frozen plasma:packed red blood cells. Demographics and outcomes of the type and quantity of resuscitative fluids used in combination with high ratio DCR were compared and analyzed. A Kaplan-Meier survival analysis was computed among four groups: colloid (median quantity = 1.0 L), <3 L crystalloid, 3–6 L crystalloid, and >6 L crystalloid. ResultsThere were 56 patients included in the analysis (28 in the crystalloid group and 28 in the colloid group). Demographics were statistically similar. Intraoperative median units of PRBC: crystalloid versus colloid groups was 13 (IQR 8-21) versus 16 (IQR 12–19), P = 0.135; median units of FFP: 12 (IQR 7–18) versus 12 (IQR 10–18), P = 0.440. OR for 10-d mortality in the crystalloid group was 8.41 [95% CI 1.65–42.76 (P = 0.01)]. Kaplan-Meier survival analysis demonstrated lowest mortality in the colloid group and higher mortality with increasing amounts of crystalloid (P = 0.029). ConclusionsDuring high ratio DCR, resuscitation with higher volumes of crystalloids was associated with an overall decreased survival, whereas low volumes of colloid use were associated with increased survival. In order to improve outcomes without diluting the survival benefit of hemostatic resuscitation, guidelines should focus on effective low volume resuscitation when high ratio DCR is used. A multi-institutional analysis is needed in order to validate these results.

Goal-directed resuscitation in the prehospital setting

The scope of prehospital (PH) interventions has expanded recently--not always with clear benefit. PH crystalloid resuscitation has been challenged, particularly in penetrating trauma. Optimal PH crystalloid resuscitation strategies remain unclear in blunt trauma as does the influence of PH hypotension. The objective was to characterize outcomes for PH crystalloid volume in patients with and without PH hypotension. Data were obtained from a multicenter prospective study of blunt injured adults transported from the scene with ISS > 15. Subjects were divided into HIGH (>500 mL) and LOW (≤500 mL) PH crystalloid groups. Propensity-adjusted regression determined the association of PH crystalloid group with mortality and acute coagulopathy (admission International Normalized Ratio, >1.5) in subjects with and without PH hypotension (systolic blood pressure [SBP], <90 mm Hg) after controlling for confounders. Of 1,216 subjects, 822 (68%) received HIGH PH crystalloid and 616 (51%) had PH hypotension. Initial base deficit and ISS were similar between HIGH and LOW crystalloid groups in subjects with and without PH hypotension. In subjects without PH hypotension, HIGH crystalloid was associated with an increase in the risk of mortality (hazard ratio, 2.5; 95% confidence interval [95% CI], 1.3-4.9; p < 0.01) and acute coagulopathy (odds ratio [OR], 2.2; 95% CI, 1.01-4.9; p = 0.04) but not in subjects with PH hypotension. HIGH crystalloid was associated with correction of PH hypotension on emergency department (ED) arrival (OR, 2.02; 95% CI, 1.06-3.88; p = 0.03). The mean corrected SBP in the ED was 104 mm Hg. Each 1 mm Hg increase in ED SBP was associated with a 2% increase in survival in subjects with PH hypotension (OR, 1.02; 95% CI, 1.01-1.03; p < 0.01). In severely injured blunt trauma patients, PH crystalloid more than 500 mL was associated with worse outcome in patients without PH hypotension but not with PH hypotension. HIGH crystalloid was associated with corrected PH hypotension. This suggests that PH resuscitation should be goal directed based on the presence or absence of PH hypotension.

Goal-directed resuscitation in the prehospital setting: A propensity-adjusted analysis

BACKGROUND: The scope of prehospital (PH) interventions has expanded recently—not always with clear benefit. PH crystalloid resuscitation has been challenged, particularly in penetrating trauma. Optimal PH crystalloid resuscitation strategies remain unclear in blunt trauma as does the influence of PH hypotension. The objective was to characterize outcomes for PH crystalloid volume in patients with and without PH hypotension. METHODS: Data were obtained from a multicenter prospective study of blunt injured adults transported from the scene with ISS > 15. Subjects were divided into HIGH (>500 mL) and LOW (<=500 mL) PH crystalloid groups. Propensity-adjusted regression determined the association of PH crystalloid group with mortality and acute coagulopathy (admission International Normalized Ratio, >1.5) in subjects with and without PH hypotension (systolic blood pressure [SBP], <90 mm Hg) after controlling for confounders. RESULTS: Of 1,216 subjects, 822 (68%) received HIGH PH crystalloid and 616 (51%) had PH hypotension. Initial base deficit and ISS were similar between HIGH and LOW crystalloid groups in subjects with and without PH hypotension. In subjects without PH hypotension, HIGH crystalloid was associated with an increase in the risk of mortality (hazard ratio, 2.5; 95% confidence interval [95% CI], 1.3–4.9; p < 0.01) and acute coagulopathy (odds ratio [OR], 2.2; 95% CI, 1.01–4.9; p = 0.04) but not in subjects with PH hypotension. HIGH crystalloid was associated with correction of PH hypotension on emergency department (ED) arrival (OR, 2.02; 95% CI, 1.06–3.88; p = 0.03). The mean corrected SBP in the ED was 104 mm Hg. Each 1 mm Hg increase in ED SBP was associated with a 2% increase in survival in subjects with PH hypotension (OR, 1.02; 95% CI, 1.01–1.03; p < 0.01). CONCLUSION: In severely injured blunt trauma patients, PH crystalloid more than 500 mL was associated with worse outcome in patients without PH hypotension but not with PH hypotension. HIGH crystalloid was associated with corrected PH hypotension. This suggests that PH resuscitation should be goal directed based on the presence or absence of PH hypotension. LEVEL OF EVIDENCE: Therapeutic study, level III.

Intra‐abdominal hypertension in the current era of modern trauma resuscitation

This study aimed to determine the incidence and outcome of post-traumatic (PT) intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) after the advances in haemostatic resuscitation. This is a prospective cohort study from January 2009-December 2011 involving patients with PT haemorrhagic shock. Patients' demographics, fluid resuscitation (<24 h) and damage control laparotomy (DCL), morbidity and mortality were assessed. Patients were divided into group 1 (no DCL) and group 2 (DCL needed). Further, group 1 was subdivided into three subgroups (IA pressure (IAP) <12, 12-20 and >20 mmHg). One hundred seventeen patients enrolled in the study (102 in group 1 and 15 in group 2) with a mean age of 35 ± 14, injury severity score (ISS) of 23 ± 10, base deficit of -8.7 ± 2.7 mmol/L, serum lactate of 4.6 ± 2.5 mg/dL and haemoglobin level of 8.8 ± 2. Patients received 7 ± 5 red blood cell units, 6 ± 4.7 fresh frozen plasma units and 8.3 ± 3 L of crystalloid per 24 h. There were significant difference between the two groups regarding crystalloid volume, blood transfusion, base deficit and intensive care unit length of stay. However, mortality was higher in group 2 (20% versus 6%). IAP ≥ 20 mmHg was reported in 16.7% patients, while 25.5% had IAP < 12 and 57.8% had IAP of 12-20 mmHg. Patients with IAP > 20 had worse metabolic acidosis and received more blood compared with other groups. One patient died because of ACS (0.9%). Overall multiorgan failure and mortality were 5 and 7.7%, respectively. With current practice of minimal fluid resuscitation and liberal use of damage control strategies among trauma patients, the IAH was common transient phenomena but the incidence of ACS is remarkably low.

Emergency department blood transfusion: the first two units are free

IntroductionStudies on blood product transfusions after trauma recommend targeting specific ratios to reduce mortality. Although crystalloid volumes as little as 1.5 L predict increased mortality after trauma, little data is available regarding the threshold of red blood cell (RBC) transfusion volume that predicts increased mortality. Materials and methodsData from a level I trauma center between January 2000 and December 2008 were reviewed. Trauma patients who received at least 100 mL RBC in the emergency department (ED) were included. Each unit of RBC was defined as 300 mL. Demographics, RBC transfusion volume, and mortality were analyzed in the nonelderly (<70 y) and elderly (≥70 y). Multivariate logistic regression was performed at various volume cutoffs to determine whether there was a threshold transfusion volume that independently predicted mortality. ResultsA total of 560 patients received ≥100 mL RBC in the ED. Overall mortality was 24.3%, with 22.5% (104 deaths) in the nonelderly and 32.7% (32 deaths) in the elderly. Multivariate logistic regression demonstrated that RBC transfusion of ≥900 mL was associated with increased mortality in both the nonelderly (adjusted odds ratio 2.06, P = 0.008) and elderly (adjusted odds ratio 5.08, P = 0.006). ConclusionsAlthough transfusion of greater than 2 units in the ED was an independent predictor of mortality, transfusion of 2 units or less was not. Interestingly, unlike crystalloid volume, stepwise increases in blood volume were not associated with stepwise increases in mortality. The underlying etiology for mortality discrepancies, such as transfusion ratios, hypothermia, or immunosuppression, needs to be better delineated.

Animal model of rapid crystalloid infusion in rats

To describe an animal model of rapid intravenous infusion with different volumes of crystalloid and discuss the clinical findings. Fifty six male Wistar rats were used, divided randomly in seven groups (n = 8). The rats of groups 1 to 6 received lactated Ringer's solution intravenously, in the rate of 25 ml/min, with different volumes proportional to blood volume (BV). The rats of group 0 were submitted to the same procedure, but did not receive the fluid (control group). The data included respiratory rate, heart rate, saturation of peripheral oxygen (SpO(2)) in two times (before and after the infusion), and upshots (respiratory arrest and death). Dunnett's test and ANOVA were used. The clinical signs significantly changed in the 2, 2.5 and 3 fold BV groups. The respiratory arrest was observed in the 1.5, 2, 2.5 and 3 fold BV groups, but death was present only in 2.5 and 3 fold BV groups. The infusion of crystalloid in the same volume of blood volume did not cause significant variation in respiratory and heart rate, saturation of peripheral oxygen and did not induce respiratory arrest. The infusion of a volume of 3 fold blood volume was lethal to all animals.

Hyperglycemic Emergencies in Adults

Hyperglycemic Emergencies in Adults

TEG-guided resuscitation is superior to standardized MTP resuscitation in massively transfused penetrating trauma patients

For nearly a decade, our center performed thromboelastograms (TEGs) to analyze coagulation profiles, allowing rapid data-driven blood component therapy. After consensus recommendations for massive transfusion protocols (MTPs), we implemented an MTP in October 2009 with 1:1:1 ratio of blood (red blood cells [RBC]), plasma (fresh-frozen plasma [FFP]), and platelets. We hypothesized that TEG-directed resuscitation is equivalent to MTP resuscitation. All patients receiving 6 units (U) or more of RBC in the first 24 hours for 21 months before and after MTP initiation in an urban Level I trauma center were examined. Demographics, mechanism of injury (MOI), Injury Severity Score (ISS), 24-hour volume of RBC, FFP, platelets, crystalloid, and 30-day mortality were compared, excluding patients with traumatic brain injuries. Variables were analyzed using Student's t-test and χ2 or Fisher's exact test. For the preMTP group, there were 165 patients. In the MTP group, there were 124 patients. There were no significant differences in ISS, age, or sex. PreMTP patients with 6U or more RBC had significantly more penetrating MOI (p = 0.017), whereas preMTP patients with 10U or more RBC had similar MOIs. All patients received less crystalloid after MTP adoption (p < 0.001). There was no difference in volume of blood products or mortality in patients receiving 6U or more RBC. Blunt trauma MTP patients who received 10U or more RBC received more FFP (p = 0.02), with no change in mortality. Penetrating trauma patients who received 10U or more RBC received a similar volume of FFP; however, mortality increased from 54.1% for MTP versus 33.3% preMTP (p = 0.04). TEG-directed resuscitation is equivalent to standardized MTP for patients receiving 6U or more RBC and for blunt MOI patients receiving 10U or more RBC. MTP therapy worsened mortality in penetrating MOI patients receiving 10U or more RBC, indicating a continued need for TEG-directed therapy. A 1:1:1 strategy may not be adequate in all patients. Therapeutic study, level IV.

Intraoperative Fluids

There is increasing evidence that intraoperative fluid therapy decisions may influence postoperative outcomes. In the past, patients undergoing major surgery were often administered large volumes of crystalloid, based on a presumption of preoperative dehydration and nebulous intraoperative 'third space' fluid loss. However, positive perioperative fluid balance, with postoperative fluid-based weight gain, is associated with increased major morbidity. The concept of 'third space' fluid loss has been emphatically refuted, and preoperative dehydration has been almost eliminated by reduced fasting times and use of oral fluids up to 2 h before operation. A 'restrictive' intraoperative fluid regimen, avoiding hypovolaemia but limiting infusion to the minimum necessary, initially reduced major complications after complex surgery, but inconsistencies in defining restrictive vs liberal fluid regimens, the type of fluid infused, and in definitions of adverse outcomes have produced conflicting results in clinical trials. The advent of individualized goal-directed fluid therapy, facilitated by minimally invasive, flow-based cardiovascular monitoring, for example, oesophageal Doppler monitoring, has improved outcomes in colorectal surgery in particular, and this monitor has been approved by clinical guidance authorities. In the contrasting clinical context of relatively low-risk patients undergoing ambulatory surgery, high-volume crystalloid infusion (20-30 ml kg(-1)) reduces postoperative nausea and vomiting, dizziness, and pain. This review revises relevant physiology of body water distribution and capillary-tissue flow dynamics, outlines the rationale behind the fluid regimens mentioned above, and summarizes the current clinical evidence base for them, particularly the increasing use of individualized goal-directed fluid therapy facilitated by oesophageal Doppler monitoring.

Preoperative and Intraoperative Predictors of Postoperative Acute Respiratory Distress Syndrome in a General Surgical Population

Acute respiratory distress syndrome (ARDS) is a devastating condition with an estimated mortality exceeding 30%. There are data suggesting risk factors for ARDS development in high-risk populations, but few data are available in lower incidence populations. Using risk-matched analysis and a combination of clinical and research data sets, we determined the incidence and risk factors for the development of ARDS in this general surgical population. We conducted a review of common adult surgical procedures completed between June 1, 2004 and May 31, 2009 using an anesthesia information system. This data set was merged with an ARDS registry and an institutional death registry. Preoperative variables were subjected to multivariate analysis. Matching and multivariate regression was used to determine intraoperative factors associated with ARDS development. In total, 50,367 separate patient admissions were identified, and 93 (0.2%) of these patients developed ARDS. Preoperative risk factors for ARDS development included American Society of Anesthesiologist status 3-5 (odds ratio [OR] 18.96), emergent surgery (OR 9.34), renal failure (OR 2.19), chronic obstructive pulmonary disease (OR 2.16), number of anesthetics during the admission (OR 1.37), and male sex (OR 1.65). After matching, intraoperative risk factors included drive pressure (OR 1.17), fraction inspired oxygen (OR 1.02), crystalloid administration in liters (1.43), and erythrocyte transfusion (OR 5.36). ARDS is a rare condition postoperatively in the general surgical population and is exceptionally uncommon in low American Society of Anesthesiologists status patients undergoing scheduled surgery. Analysis after matching suggests that ARDS development is associated with median drive pressure, fraction inspired oxygen, crystalloid volume, and transfusion.

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Introduction: Fluid resuscitation of burn patients is critical during the initial 48 hours post burn. Inappropriate fluid management of the burn patient may result in over or under resuscitation leading to serious complications and death. Hypothesis: The use of a computerized decision support system (CDSS) for fluid resuscitation of burn patients is able to maintain patients within appropriate resuscitation targets. Methods: We performed a retrospective cohort review of 207 patients admitted to our burn intensive care unit (BICU) from December 2007 to June 2012. Inclusion criteria included requirement for active fluid resuscitation as defined by a total body surface area (TBSA) greater than 20%. Patients were resuscitated using a custom CDSS. The system provides crystalloid recommendations every hour post admission based on a target urinary output (UOP) of 30 to 50 ml/hr, and providers are free override the system’s recommendations at any time. Average crystalloid volume of fluid infused per hour was analyzed and compared to predicted volumes based on the Modified Brooke (MB) resuscitation formula (2 ml/kg/TBSA) and Parkland (PK) resuscitation formula (4 ml/kg/TBSA) during the initial 24 hours post burn. UOP was also analyzed for meeting target rates during the resuscitation period. Results: Mean cohort age was 44 ± 21 years with an average weight of 89 ± 61 kg. Mean TBSA burn was 41 ± 19% including an average of 17 ± 22% full thickness. Average total fluid administered during the initial 24 hours (11.1 ± 6.4 L) was significantly higher than MB (7.1 ± 4.6 L, p<0.01) and lower than PK (14.2 ± 9.1 L, p<0.01) with a normalized volume of 3.49 ± 1.95 ml/kg/TBSA. Total resuscitation volume during the initial 8 hours was not significantly different from the expected MB volume (3.4 ± 2.7 L vs. 3.5 ± 2.3 L, p=0.40) but was significantly lower than the expected PK volume (3.4 ± 2.7 L vs. 7.1 ± 4.6 L, p<0.01). Total volume during the second 16 hours (7.7 ± 4.8 L) was significantly higher than MB (3.5 ± 2.2 L, p<0.01), but was not different from the expected PK volume (7.1 ± 4.6 L, p=0.13). Mean UOP for the initial 24 hours was 55 ± 28 ml/hr with a median value of 49 ml/hr and mean rate of 0.66 ± 36 ml/hr/kg. Quartile analysis resulted in 50% of UOP values occurring between 36 ml/hr and 68 ml/hr. Conclusions: Use of our CDSS resulted in average crystalloid volumes bounded between the lower MB and the upper PK formulas while maintaining appropriate UOP values. This analysis shows that implementation of a CDSS can be an effective tool for care of patients in the critical care environment.

The Effects of QuikClot Combat Gauze, Fluid Resuscitation, and Movement on Hemorrhage Control in a Porcine Model

The purpose of this study was to compare the effectiveness of QuikClot Combat Gauze (QCG) compared to a control group on hemorrhage control; the amount of crystalloid volume infusion on rebleeding; the effect of movement on hemorrhage. This was a prospective, experimental design. Swine were randomly assigned to either the QCG () or the control group (). Investigators transected the femoral artery and vein in each swine. After one minute of uncontrolled hemorrhage, the hemostatic agent, QCG, was placed into the wound followed by standard wound packing. The control group underwent the same procedures but without a hemostatic agent. After five minutes of direct pressure, a standard pressure dressing was applied. After 30 minutes, dressings were removed, and the wound was observed for rebleeding for 5 minutes. If hemostasis occurred, 5 liters of crystalloid was given over 5 minutes, and the wound was observed for rebleeding for 5 additional minutes. If no bleeding occurred, the extremity on the side of the injury was moved. There were significant differences in the amount of hemorrhage (), the amount of fluid administration (), and the number of movements () between the QCG and control.

Predictors of Immediate Tracheal Extubation in the Operating Room after Pediatric Liver Transplantation

Introduction: Pediatric orthotopic liver transplant (OLT) recipients frequently need mechanical ventilation during the immediate posttransplant period. However, intensive care unit beds are costly and scarce, and therefore it is important to anticipate the patients who will require postoperative mechanical ventilation support. In addition immediate postoperative extubation may reduce the incidence of postoperative respiratory complications and improve patient outcome after OLT. In this study we aimed to determine the predictors of mechanical ventilation need after OLT in pediatric patients. Methods: The records of 57 pediatric patients who underwent OLT, performed by the same team in the Baskent University Hospital from April 1990 to August 2009, were retrospectively analyzed. The patients were divided into two groups according to whether they required postoperative mechanical ventilation or not. Collected data included demographic features, co-morbidities, etiology of the liver failure, perioperative laboratory values, intraoperative hemodynamic parameters, use and volume of crystalloids, colloids, blood products and albumin, portal vein clamping time, requirement of inotropes, vasopressors, and duration of anesthesia. Results: The mean age and body weight of the patients were 25.0±23.1 months and 10.8±5.3 kg, respectively. Out of 57 patients, 26 (46%) needed postoperative mechanical ventilation. Compared with those who did not require postoperative mechanical ventilation those who did had growth failure (P=.03), higher mean intraoperative lactate level (P=.03), higher mean intraoperative fresh frozen plasma and erythrocyte suspension requirement per kg (P=.049), and intraoperative vasopressor requirement (P=.022). Multivariate logistic regression analysis revealed that growth failure (odds ratio, 37; P=.03) and a higher intraoperative lactate level (odds ratio, 1.5; P=.03) were predictors of mechanical ventilation need in these patients. Conclusion: 46% of our pediatric OLT recipients required mechanical ventilation postoperatively. Growth failure and higher intraoperative lactate levels were associated with postoperative mechanical ventilation need in our patients.

The Effect of Preoperative Recombinant Erythropoietin on Postoperative Hematocrit Level After Orthognathic Surgery

To compare the postoperative red cell mass as indicated by the hematocrit value of orthognathic surgery patients given iron supplementation and a single preoperative dose of erythropoietin alpha (EPO) and patients who did not receive either EPO or iron supplementation. Subjects who had a Le Fort I osteotomy (LFI) or a combination of LFI and bilateral sagittal split osteotomy between 2005 and 2008 and were aged at least 13 years were included. Subjects were excluded if they had a history of maxillofacial trauma, a craniofacial syndrome, or a major systemic medical condition. Subjects either had EPO administered with iron supplements before surgery (surgeon A protocol) or received neither (surgeon B protocol). Venous blood samples were taken, in accordance with clinic protocol, before surgery (before administration of EPO) and on postoperative day 1. Multiple linear regression with backward selection was used to analyze the change in hematocrit value. Explanatory variables included group, preoperative hematocrit level, age, gender, length of surgery, blood loss, and crystalloid (fluid replacement) volume. The study included 178 eligible patients: 86 (48%) had a combination of LFI and bilateral sagittal split osteotomy and 92 (52%) had an isolated LFI. Of the patients, 114 (64%) had EPO/iron supplements administered before surgery whereas 64 did not. The mean change in hematocrit level as an indicator of the change in red cell mass was statistically significantly different (P = .01) for the subjects who received preoperative administration of EPO with iron supplementation compared with those who did not receive EPO plus iron. The administration of EPO plus iron was protective: the decrease in hematocrit level after surgery was smaller for subjects in the EPO group even after we controlled for age, gender, preoperative hematocrit level, length of surgery, blood loss, and crystalloid (fluid replacement) volume. A single preoperative dose of erythropoietin with iron supplementation resulted in a smaller decrease, on average, in postoperative red cell mass as indicated by hematocrit value in patients with complicated orthognathic surgery procedures.

Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration

Hyperfibrinolysis (HF) has been reported to occur in a range of 2% to 34% of trauma patients. Using rapid thromboelastography (r-TEG), we hypothesized that HF is (1) rarely present at admission on patients with severe injury and (2) associated with crystalloid hemodilution. To further strengthen this hypothesis, we created an in vitro hemodilution model to improve our mechanistic understanding of the early HF. The trauma registry was queried for patients who were our highest-level trauma activations and admitted directly from the scene (October 2009-October 2010). HF was defined as more than 7.5% amplitude reduction 30 minutes after maximal amplitude (LY30). Using r-TEG, we then created an in vitro hemodilution model (0.9% NS) with and without tissue injury (addition of tissue factor and tissue plasminogen activator) to identify crystalloid volumes and injury needed to achieve specific LY30 values. Admission r-TEG values were captured on 1996 consecutive admissions. Only 41 patients (2%) had HF at admission r-TEG. The groups were similar in demographics. Compared with patients without HF, the HF group had more prehospital crystalloid (1.5 vs. 0.5 L), higher median Injury Severity Score (25 vs. 16), greater admission base deficit (20 vs. 2), and higher mortality (76% vs. 10%); all p < 0.001. Controlling for Injury Severity Score and base deficit on arrival, prehospital fluid was associated with a significant increase in likelihood of HF. In fact, each additional liter of crystalloid was associated with a 15% increased odds of HF. The in vitro model found that hemodilution to 15% of baseline and tissue factor + tissue plasminogen activator was required to achieve an LY30 of 50%. Although uncommon immediately after injury, HF is associated with prehospital crystalloid administration and shock at admission and is highly lethal. Our in vitro model confirms that tissue injury and significant crystalloid hemodilution result in severe and immediate HF.

Crystalloid vs. hypertonic crystalloid–colloid solutions for induction of mild therapeutic hypothermia after experimental cardiac arrest

PurposeTo compare cerebral and hemodynamic consequences of different volumes of cold acetated Ringer's solution or cold hypertonic saline dextran administered in order to achieve mild hypothermia after cardiac arrest (CA) in a pig model of experimental cardiopulmonary resuscitation (CPR). MethodsUsing an experimental pig model of 12min CA (followed by 8min CPR or no resuscitation) we compared four groups of piglets: a control group, a normothermic group and two groups with different solutions administered for induction of hypothermia. The control group of 5 piglets underwent 12min CA without subsequent CPR, after which the brain of the animals was removed immediately. After restoration of spontaneous circulation (ROSC) the resuscitated piglets were randomized into a normothermic group (NT group=10), and two hypothermic groups that received cold infusions of either 30mL/kg acetated Ringer's solution (Much fluid group, M, n=10) or 3mL/kg hypertonic saline dextran solution (Less fluid group, L, n=10), respectively, administered during 30min. Additional external cooling with ice packs was used in hypothermic groups. Sixty or 180min after ROSC the experiment was terminated. Immediately after arrest the brain was removed for histological analyses. ResultsThe median time to reach the target core temperature of 34°C after ROSC was 51.5±7.8min in L group and 48.8±8.6min in M group. Less cerebral tissue content of water (p<0.001), sodium (p<0.0001), potassium (p<0.0001) and less central venous pressure (CVP) at 5 and 15min after ROSC were demonstrated in L group. Increased brain damage was demonstrated over time in NT group (p<0.001). Less neurologic damage and BBB disruptions (albumin leakage) was observed at 180min in M group in comparison with both NT and L groups (p<0.001). ConclusionNo statistical differences were observed between the hypothermic groups in the time to achieve mild hypothermia. Although inclusion of cold hypertonic crystalloid–colloidal solutions in the early resuscitation after ROSC may be more effective than cold crystalloids in reducing brain edema, this study demonstrates that mild hypothermia induced with small volumes of cold hypertonic crystalloid–colloids is less as effective as crystalloid's induced hypothermia in mitigating brain injury after cardiac arrest.

Coagulopathy Management in Liver Transplantation

Risk of bleeding and transfusion in liver transplantation is determined by age, severity of liver disease, as well as hemoglobin and plasma fibrinogen values. During the hepatectomy and the anhepatic phase, the coagulopathy is related to a decrease in clotting factors caused by surgical bleeding, facilitated by the increased portal hypertension and esophageal-gastric venous distension. Corrections of hematologic disturbances by administration of large volumes of crystalloid, colloid, or blood products may worsen the coagulopathy. Also, impaired clearance of fibrinolytic enzymes released from damaged cells can lead to primary fibrinolysis. At time of graft reperfusion further deterioration may occur as characterized by global reduction among all coagulation factors, decreased plasminogen activator inhibitor factors, and simultaneous generation of tissue plasminogen activator. In situations with inherent risk of bleeding, hypofibrinogenemia must be corrected. Concern about unwanted events is a major limitation of preventive therapy. There is some evidence for the efficacy of antifibrinolytic drugs to reduce red blood cell requirements. A guide for antifibrinolytic therapy are clot firmness in trhomboelastometry or alternatively, diffuse bleeding associated to a fibrinogen value less than 1 g/L. Because thrombin generation is limited in severe thrombocytopenia, platelet administration is recommended when active bleeding coexists with a platelet count below 50,000/mm3. When the administration of hemoderivates and antifibrinolytic drugs does not correct severe bleeding, consumption coagulopathy and secondary fibrinolysis should be suspected. Treatment of affected patients should be based upon correcting the underlying cause, mostly related to tissue hypoxia due to critical hypoperfusion.

Reply

Sir:FigureWe thank Dr. Otiv for the Letter to the Editor regarding our article featured in the December issue of the Journal, entitled “Intravenous Fluid Infusion Rate in Microsurgical Breast Reconstruction: Important Lessons Learned from 354 Free Flaps” (Plast Reconstr Surg. 2011;128:1153–1160). Most of your queries are outlined in the multivariable analysis section in the article, including Table 3 and the plot in Figure 1; however, we understand that your questions were based on access to the abstract alone and unfortunately all of the information could not be conveyed in the abstract. Please refer to our responses to your queries below: Odds ratio (Table 4). Confidence interval of the odds ratio (Table 4). Whether crystalloid infusion rate was used as a numerical/categorical variable and whether it was the latter, whether dummy variables were used and different nominal variables for the extremes were used. Fig. 1: A parabolic relationship was found between crystalloid infusion volume and complications. Reprinted from Zhong T, Neinstein R, Massey C, et al. Intravenous fluid infusion rate in microsurgical breast reconstruction: Important lessons learned from 354 free flaps. Plast Reconstr Surg. 2011;128:1153–1160.Table 4: Multivariate Analysis of Factors Associated with Postoperative ComplicationsThe crystalloid infusion rate was used as a continuous variable in the units of milliliters per kilogram per 24 hours. Below are the formulas used for calculating the estimated probability of complication based on crystalloid and time under anesthesia (–2.8550 is the intercept from the logistic model). It is important to note that the model is based on a data set with only 54 events, so it is not recommended that someone use it to try to predict the likelihood of a complication, as there would be a lot of uncertainty surrounding these probabilities. Toni Zhong, F.R.S.C.(C.), M.H.S. Stefan O. P. Hofer, M.D., Ph.D. University Health Network, Toronto, Ontario, Canada DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication.

The Median Effective Volume of Crystalloid in Preventing Hypotension in Patients Undergoing Cesarean Delivery with Spinal Anesthesia

Spinal anesthesia-associated maternal hypotension in Cesarean delivery is the most frequent and troublesome complication, posing serious risks to mothers and compromising neonatal well-being. The effective volume of intravenous crystalloid as the preventive strategy in this context has not been estimated. Eighty-five parturients with ASA physical status I/II undergoing elective Cesarean delivery were screened and 67 eligible women were assigned to receive pre-spinal crystalloid loading. Hyperbaric 0.5% bupivacaine 2mL (10mg) plus morphine 50μg was given to all patients. The volume of crystalloid was determined by an up-and-down sequential method. The crystalloid was infused at a rate of 100-150mL.min(-1) prior to the spinal anesthetic injection. The initial volume of crystalloid was 5mL.kg(-1). Volume-effect data were fitted to a sigmoidal maximum efficacy model and the median effective volume (EV(50)) and corresponding 95% confidence interval (95% CI) were estimated using maximum likelihood estimation and logistic regression with Firth's correction. A total of 67 subjects completed the study and were analyzed. Twenty-eight (41.8%) patients developed hypotension with their systolic blood pressure (SBP) decreasing > 20% of baseline. The EV(50) of crystalloid were 12.6mL.kg(-1) (95% CI, 11.6 to 14.8mL.kg(-1)). With Firth's correction, the pooled probability of an effective preventive volume of crystalloid at 13mL.kg(-1) was 50.2% (95% CI, 30% to 83.1%). The estimated EV(50) of the preloaded crystalloid required to prevent spinal anesthesia-induced hypotension in a Cesarean section is, approximately, 13mL.kg(-1). However, prophylactic or therapeutic vasoconstrictors should also be prepared and administered at an appropriate time.