Effect of Hypothermia on the Coagulation Cascade

ArticleinCritical Care Medicine 20(10):1402-5 · October 1992with 608 Reads
Cite this publication
Abstract
The development of a multifactorial coagulopathy after massive transfusion is a well-recognized clinical problem that is almost always accompanied by hypothermia. The purpose of this study was to investigate the isolated effect of alterations of temperature on the integrity of the coagulation cascade. Prothrombin times and partial thromboplastin times were each performed 15 times on samples of pooled normal plasma at the temperatures of 37 degrees C, 34 degrees C, 31 degrees C, and 28 degrees C, as well as 39 degrees C and 41 degrees C. Mean prothrombin time results increased from 11.8 +/- 0.3 (SD) secs at 37 degrees C to 12.9 +/- 0.5, 14.2 +/- 0.5, and 16.6 +/- 0.2 secs at 34 degrees C, 31 degrees C, and 28 degrees C, respectively (p < or = .001 for each). Partial thromboplastin time determinations increased from 36.0 +/- 0.7 (SD) secs at 37 degrees C to 39.4 +/- 1.0, 46.1 +/- 1.1, and 57.2 +/- 0.6 secs at 34 degrees C, 31 degrees C, and 28 degrees C, respectively (p < or = .001 for each). Both prothrombin time and partial thromboplastin time determinations were only minimally shortened at hyperthermic temperatures. The series of enzymatic reactions of the coagulation cascade are strongly inhibited by hypothermia, as demonstrated by the dramatic prolongation of prothrombin time and partial thromboplastin time tests at hypothermic deviations from normal temperature in a situation where factor levels were all known to be normal. Clinicians who deal with critically ill massively transfused hypothermic patients all recognize the inevitable appearance of a coagulopathy that has a multifactorial origin. Unless specifically considered, the contribution of hypothermia to the hemorrhagic diathesis may be overlooked since coagulation testing is performed at 37 degrees C, rather than at the patient's actual in vivo temperature.

Do you want to read the rest of this article?

Request full-text
Request Full-text Paper PDF
  • Article
    Full-text available
    Background: We determined the impact of intraoperative hypothermia on postoperative bleeding after thoracic aortic surgery. Methods: We retrospectively analyzed 98 consecutive patients who underwent aortic surgery with deep hypothermic circulatory arrest between 2010 and 2014. We evaluated lowest temperature, absolute decrease in temperature, and rewarming rate. Univariate and multivariate regression were used to determine relationships between temperature, clinical characteristics, and measures of postoperative bleeding. Results: The mean age of patients was 60.5 ± 15.1 years, with 64.3% male and 60% Caucasian. The lowest temperatures recorded were 13.5 ± 4.6°C at the bypass circuit. Change in hematocrit was associated with ethnicity, preoperative hematocrit, and rewarming rate. Chest tube output was associated with body mass index, preoperative platelet count, prior cardiac surgery, cardiopulmonary bypass (CPB) duration, intraoperative blood product transfusion, lowest surface temperature, and change in surface temperature. Postoperative packed red blood cell transfusion was associated with ejection fraction, chronic obstructive pulmonary disease (COPD), platelet count, partial thromboplastin time, CPB duration, and lowest blood temperature. Fresh frozen plasma transfusion correlated with COPD, CPB duration, and final blood temperature. Platelet transfusion correlated with body mass index and preoperative platelet count. Unplanned reoperation for bleeding was associated with final temperature and change in temperature. Conclusion: We found no consistent associations between intraoperative temperature and indicators of bleeding. Intraoperative cooling strategies should be based on optimal end-organ protection rather than fear of postoperative bleeding; rewarming strategies may ameliorate the risk of coagulopathy.
  • Article
    Full-text available
    Background: General anesthesia may induce inadvertent hypothermia and this may be related to perioperative cardiovascular complications. Microvascular reactivity, measured by the recovery slope during a vascular occlusion test, is decreased during surgery and is also related to postoperative clinical outcomes. We hypothesized that microvascular changes during surgery may be related to intraoperative hypothermia. To evaluate this, we conducted a randomized study in patients undergoing off-pump coronary artery bypass surgery, in which the effect of prewarming on microvascular reactivity was evaluated. Methods: Patients scheduled for off-pump coronary artery bypass surgery were screened. Enrolled patients were randomized to the prewarming group to receive forced-air warming during induction of anesthesia or to the control group. Measurement of core and skin temperatures and vascular occlusion test were conducted before anesthesia induction, 1, 2, and 3 h after induction, and at the end of surgery. Results: In total, 40 patients were enrolled and finished the study (n = 20 in the prewarming group and n = 20 in the control group). During the first 3 h of anesthesia, core temperature was higher in the prewarming group than the control group (p < 0.001). The number of patients developing hypothermia was lower in the prewarming group than the control group (4/20 vs. 13/20, p = 0.004). However, tissue oxygen saturation and changes in recovery slope following a vascular occlusion test at 3 h after anesthesia induction did not differ between the groups. There was no difference in clinical outcome, including perioperative transfusion, wound infection, or hospital stay, between the groups. Conclusions: Prewarming during induction of anesthesia decreased intraoperative hypothermia, but did not reduce the deterioration in microvascular reactivity in patients undergoing off-pump coronary artery bypass surgery. Trial registration: ClinicalTrials.gov NCT02186210.
  • Article
    Full-text available
    Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartmentsyndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangementsand multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinicalsituations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source ofinfection or the necessity to re-explore (as a“planned second-look”laparotomy) or complete previously initiateddamage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-traumapatients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuriesor critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consumingand represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only beconsidered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as thepatient can physiologically tolerate it. All precautions to minimize complications should be implemented.
  • Article
    Full-text available
    IntroductionAn 88-year-old woman suffered a cerebrovascular accident and was found on the floor of her cold house.Materials and methodsAt the time of admission to our division, the patient was unresponsive with a rectal temperature of 28 °C, blood pressure of 120/80 mmHg, and a heart rate of 40 bpm. The cerebral CT revealed a hypodense lesion in the temporal region. The ECG showed sinus bradycardia, prolonged PR and QTc intervals, and a classic “J” (Osborn) wave that was most pronounced in the lateral and inferior leads. The patient presented a low respiratory rate, hypoventilation, severe acidosis (both respiratory and metabolic), hyperkalemia, elevated liver enzymes, mild anemia, hyporeflexia, and sluggish pupil responses.ResultsDuring rewarming with thermic blanket and heated intravenous fluids, the respiratory condition improved, and the ECG alterations disappeared. Twenty-four hours later, however, the patient died suddenly due to cardiac asystole.DiscussionThis report analyses the effects of hypothermia and its clinical manifestations and provides a brief discussion of the electrophysiologic mechanisms underlying Osborn waves and the other electrocardiographic changes associated with hypothermia.
  • Article
    Background: Accidental hypothermia concerns a body core temperature of less than 35°C without a primary defect in the thermoregulatory system. It is a serious threat to prehospital patients and especially injured patients, since it can induce a vicious cycle of the synergistic effects of hypothermia, acidosis and coagulopathy; referred to as the trauma triad of death. To prevent or manage deterioration of a cold patient, treatment of hypothermia should ideally begin prehospital. Little effort has been made to integrate existent literature about prehospital temperature management. The aim of this study is to provide an up-to-date systematic overview of the currently available treatment modalities and their effectiveness for prehospital hypothermia management. Data sources: Databases PubMed, EMbase and MEDLINE were searched using the terms: "hypothermia", "accidental hypothermia", "Emergency Medical Services" and "prehospital". Articles with publications dates up to October 2017 were included and selected by the authors based on relevance. Results: The literature search produced 903 articles, out of which 51 focused on passive insulation and/or active heating. The most effective insulation systems combined insulation with a vapor barrier. Active external rewarming interventions include chemical, electrical and charcoal-burning heat packs; chemical or electrical heated blankets; and forced air warming. Mildly hypothermic patients, with significant endogenous heat production from shivering, will likely be able to rewarm themselves with only insulation and a vapor barrier, although active warming will still provide comfort and an energy-saving benefit. For colder, non-shivering patients, the addition of active warming is indicated as a non-shivering patient will not rewarm spontaneously. All intravenous fluids must be reliably warmed before infusion. Conclusion: Although it is now accepted that prehospital warming is safe and advantageous, especially for a non-shivering hypothermic patient, this review reveals that no insulation/heating combinations stand significantly above all the others. However, modern designs of hypothermia wraps have shown promise and battery-powered inline fluid warmers are practical devices to warm intravenous fluids prior to infusion. Future research in this field is necessary to assess the effectiveness expressed in patient outcomes.
  • Article
    Full-text available
    Traumatic injury is one of the leading causes of death, with uncontrolled hemorrhage from coagulation dysfunction as one of the main potentially preventable causes of the mortality. Hypothermia, acidosis, and resuscitative hemodilution have been considered as the significant contributors to coagulation manifestations following trauma, known as the lethal triad. Over the past decade, clinical observations showed that coagulopathy may be present as early as hospital admission in some severely injured trauma patients. The hemostatic dysfunction is associated with higher blood transfusion requirements, longer hospital stay, and higher mortality. The recognition of this early coagulopathy has initiated tremendous interest and effort in the trauma community to expand our understanding of the underlying pathophysiology and improve clinical treatments. This review discusses the current knowledge of coagulation complications following trauma.
  • Article
    Objective: Transfusion is a key treatment for patients with hemorrhage. Early massive transfusion (EMT) is defined as transfusion of 10 or more units of red blood cells (RBC) within the first 6 hours. We attempted to determine whether metabolic markers can be used as predictors for EMT. Method: We retrospectively reviewed outcomes in 71 patients who visited the emergency department within 12 hours after trauma and received at least 1 unit of RBC within 24 hours between January 2008 and June 2010. Results: Of the 71 patients, 54 were male and 17 were female; their mean age was 50.3 +/- 17.7 years. Of these, 15 required EMT and 56 did not; these patients received 17.7 +/- 13.1 and 2.8 +/- 2.3 units of RBCs, respectively. There were significant differences between EMT and non-EMT groups in injury severity score (ISS; p=0.001), systolic blood pressure (SBP; p=0.010), base deficit (p=0.003), and lactate >= 3.5 concentration (p=0.001). Logistic regression analysis showed that SBP <90 mmHg (odds ratio [OR] 11.71, 95% CI 1.83-74.77, p=0.009), ISS >= 25(OR 23.39, 95% CI 1.87-293.23, p=0.015), and lactate mmol/L (OR 6.99, 95% CI 1.10-44.33, p=0.039) were significant predictors of EMT. The area under the curve for >= 3.5mmol/L lactate was 0.79 (p=0.001), with a sensitivity of 76.7% and a specificity of 67.8%. The 30-day mortality rate was significantly higher in patients with lactate >= 3.5mmol/L than in those with lactate <3.5 mmol/L (p=0.002). Conclusion: Lactate concentration is an important predictor of the need for EMT and should be considered in the initial phase of trauma resuscitation to prepare for massive transfusion.
  • Article
    Full-text available
    Abstract Background Inadvertent perioperative hypothermia (IPH) leads to surgical complications and increases length of stay. IPH rates are high with the current standard of care, forced air warming (FAW). Our hypothesis is that a prototype thermal compression device that heats the popliteal fossa and soles of the feet, with lower leg compression, increases perioperative temperatures and reduces IPH compared to the current standard of care. Methods Thirty six female breast surgery patients, at a tertiary academic hospital, were randomized to the device or intraoperative FAW (stage I) with a further 18 patients randomized to the device with a single heating area only (stage II, popliteal fossa or sole of the feet). Stage I: 37 patients recruited (final 36). Stage II: 18 patients recruited (final 18). Inclusion criteria: general anesthesia with esophageal monitoring for over 30 min, legs available and able to fit the device and no contraindications to leg heating or compression. The intervention was: Stage I: Investigational prototype thermal compression device (full device group) or intraoperative FAW. Stage II: Device with only a single heating location. Primary outcomes were perioperative temperatures and incidence of IPH. Secondary outcomes were local skin temperature, general and thermal comfort scores and presence of perioperative complications, including blood loss. Results Mean temperatures in the full device group were significantly higher than the FAW group in the pre-operative (36.7 vs 36.4 °C, p
  • Article
    Full-text available
    Limited evidence is available regarding the correlation between intraoperative hypothermia and perioperative complications in shoulder arthroplasty. The purpose of this study was to determine the incidence of intraoperative hypothermia in patients treated with shoulder arthroplasty and its effect on perioperative complications. A retrospective chart review was performed on 657 consecutive patients who underwent shoulder arthroplasty at a single institution between August 2013 and June 2016. Demographic data, surgery-specific data, postoperative complications, length of stay, and 30-day read-mission were recorded. Patients were classified as hypothermic if their mean intraoperative temperature was less than 36°C. Statistical analyses with univariate and multivariate logistic regression were performed to evaluate the association of intraoperative hypothermia with perioperative complications. The incidence of intraoperative hypothermia in shoulder arthroplasty was 52.7%. Increasing age (P=.002), lower body mass index (P=.006), interscalene anesthetic (P=.004), and lower white blood cell count (P<.001) demonstrated increased association with hypothermia. Longer operating room times and increased estimated blood loss were not found to be associated with intraoperative hypothermia. Hypothermia demonstrated no significant association with surgical site infections nor any other perioperative complications. Patients undergoing shoulder arthroplasty showed a high incidence of intraoperative hypothermia. Lower body mass index, increasing age, interscalene anesthetic, and lower white blood cell count were associated with an increased incidence of hypothermia. Contrary to previous studies, intraoperative hypothermia was not found to contribute to perioperative complications in shoulder arthroplasty. [Orthopedics. 201x; xx(x):xx-xx.].
  • Article
    Full-text available
    Background Perioperative thermal disturbances during orthotopic liver transplantation (OLT) are common. We hypothesized that in patients undergoing OLT the use of a humidified high flow CO2 warming system maintains higher intraoperative temperatures when compared to standardized multimodal strategies to maintain thermoregulatory homeostasis. Methods We performed a randomized pilot study in adult patients undergoing primary OLT. Participants were randomized to receive either open wound humidification with a high flow CO2 warming system in addition to standard care (Humidification group) or to standard care alone (Control group). The primary end point was nasopharyngeal core temperature measured 5 min immediately prior to reperfusion of the donor liver (Stage 3 − 5 min). Secondary endpoints included intraoperative PaCO2, minute ventilation and the use of vasoconstrictors. ResultsEleven patients were randomized to each group. Both groups were similar for age, body mass index, MELD, SOFA and APACHE II scores, baseline temperature, and duration of surgery. Immediately prior to reperfusion (Stage 3 − 5 min) the mean (SD) core temperature was higher in the Humidification Group compared to the Control Group: 36.0 °C (0.13) vs. 35.4 °C (0.22), p = 0.028. Repeated measured ANOVA showed that core temperatures over time during the stages of the transplant were higher in the Humidification Group compared to the Control Group (p < 0.0001). There were no significant differences in the ETCO2, PaCO2, minute ventilation, or inotropic support. Conclusion The humidified high flow CO2 warming system was superior to standardized multimodal strategies in maintaining normothermia in patients undergoing OLT. Use of the device was feasible and did not interfere with any aspects of surgery. A larger study is needed to investigate if the improved thermoregulation observed is associated with improved patient outcomes. Trial registrationACTRN12616001631493. Retrospectively registered 25 November 2016.
  • Article
    Full-text available
    Background Guidance for the management of thermal injuries has evolved with improved understanding of burn pathophysiology. Guidance for the management of cold burn injuries is not widely available. The management of these burns differs from the standard management of thermal injuries. This study aimed to review the etiology and management of all cold burns presenting to a large regional burn centre in the UK and to provide a simplified management pathway for cold burns. Methods An 11-year retrospective analysis (1 January 2003–31 December 2014) of all cold injuries presenting to a regional burns centre in the UK was conducted. Patient case notes were reviewed for injury mechanism, first aid administered, treatment outcomes and time to healing. An anonymized nationwide survey on aspects of management of cold burns was disseminated between 13 July 2015–5 October 2015 to British Association of Plastic Reconstructive and Aesthetic Surgeons (BAPRAS) and Plastic Surgery Trainees Association (PLASTA) members in the UK. Electronic searches of MEDLINE, EMBASE and the Cochrane Library were performed to identify relevant literature to provide evidence for a management pathway for cold burn injuries. Results Twenty-three patients were identified. Age range was 8 months–69 years. Total body surface area (TBSA) burn ranged from 0.25 to 5 %. Twenty cases involved peripheral limbs. Seventeen (73.9 %)cases were accidental, with the remaining six (26.1 %) cases being deliberate self-inflicted injuries. Only eight patients received first aid. All except one patient were managed conservatively. One case required skin graft application due to delayed healing. We received 52 responses from a total of 200 questionaires. Ninety percent of responders think clearer guidelines should exist. We present a simplified management pathway based on evidence identified in our literature search. Conclusions Cold burns are uncommon in comparison to other types of burn injuries. In the UK, a disproportionate number of cold burn injuries are deliberately self-inflicted, especially in the younger patient population. Our findings reflect a gap in clinical knowledge and experience. We proposed a simplified management pathway for managing cold burn injuries, consisting of adequate first aid using warm water, oral prostaglandin inhibitors, deroofing of blisters and topical antithromboxane therapy. Electronic supplementary material The online version of this article (doi:10.1186/s41038-016-0060-x) contains supplementary material, which is available to authorized users.
  • Article
    Full-text available
    Objective: To evaluate the hemostatic system in patients undergoing surgery for acute type A aortic dissection (ATAAD) compared with those undergoing elective aortic procedures. Design: This was a prospective, observational study. Setting: The study was performed at a single university hospital. Participants: Twenty-five patients with ATAAD were compared with 20 control patients undergoing elective surgery of the ascending aorta or the aortic root. Interventions: No interventions were performed. Measurements and Main Results: Platelet count and levels of fibrinogen, D-dimer, prothrombin time/international normalized ratio, activated partial thromboplastin time, and antithrombin were analyzed perioperatively and compared between the 2 groups. Patients with ATAAD had lower preoperative levels of platelets (188 [156-217] × 10 ⁹ /L v 221 [196-240] × 10 ⁹ /L; p = 0.018), fibrinogen (1.9 [1.6-2.4] g/L v 2.8 [2.2-3.0] g/L; p = 0.003), and antithrombin (0.81 [0.73-0.94] kIU/L v 0.96 [0.92-1.00] kIU/L; p = 0.003) and significantly higher levels of D-dimer (2.9 [1.7-9.7] mg/L v 0.1 [0.1-0.2] mg/L; p < 0.001) and prothrombin time/international normalized ratio (1.15 [1.1-1.2] v 1.0 [0.93-1.0]; p = 0.001). Surgery caused significant changes of the coagulation system in both groups. Intraoperative bleeding volumes were larger in the ATAAD group (2,407 [1,804-3,209] mL v 1,212 [917-1,920] mL; p < 0.001), and patients undergoing ATAAD surgery received significantly more transfusions of red blood cells (2.5 [0.25-4.75] U v 0 [0-2.75] U; p = 0.022), platelets (4 [3.25-6] U v 2 [2-4] U; p = 0.002), and plasma (2 [0-4] U v 0 [0-0] U; p = 0.004) compared with the elective group. Conclusions: This study demonstrates that ATAAD is associated with a coagulopathic state. Surgery causes additional damage to the hemostatic system in ATAAD patients, but also in patients undergoing elective surgery of the ascending aorta or the aortic root.
  • Article
    Full-text available
    Hypothermia is present in up to two-thirds of patients with severe injury, although it is often disregarded during the initial resuscitation. Studies have revealed that hypothermia is associated with mortality in a large percentage of trauma cases when the patient’s temperature is below 32 °C. Risk factors include the severity of injury, wet clothing, low transport unit temperature, use of anesthesia, and prolonged surgery. Fortunately, associated coagulation disorders have been shown to completely resolve with aggressive warming. Selected passive and active warming techniques can be applied in damage control resuscitation. While treatment guidelines exist for acidosis and bleeding, there is no evidence-based approach to managing hypothermia in trauma patients. We synthesized a goal-directed algorithm for warming the severely injured patient that can be directly incorporated into current Advanced Trauma Life Support guidelines. This involves the early use of warming blankets and removal of wet clothing in the prehospital phase followed by aggressive rewarming on arrival at the hospital if the patient’s injuries require damage control therapy. Future research in hypothermia management should concentrate on applying this treatment algorithm and should evaluate its influence on patient outcomes. This treatment strategy may help to reduce blood loss and improve morbidity and mortality in this population of patients.
  • Article
    Full-text available
    Congenital heart disease (CHD) is the most common form of congenital abnormality and occurs in over 1% of newborns. Approximately 30% of children with CHD have other extra-cardiac anomalies, which significantly increases mortality in CHD patients. It is expected that the number of CHD patients who consult non-specialized hospitals for non-cardiac surgery after palliative or corrective operations has increased because of the extraordinary progression of treatments, such as surgical procedures, interventional procedures, and intensive care medicine, as well as diagnosis. The aim of this article is to enable anaesthesiologists who are not usually engaged in the anaesthesia management of CHD patients to provide perioperative management for CHD patients safely and with confidence by having basic and advanced knowledge about CHD patients and their pathophysiological characteristics.
  • Article
    The importance of preventing hypothermia in the perioperative period cannot be overemphasised. The use of active warming devices is advocated and practised widely. The forced-air warming (FAW) blanket is currently a popular modality. The BARRIER® EasyWarm® (Mölnlycke Healthcare, Belrose, Australia) self-heating blanket, which does not require a power unit, has been proposed as an easy-to-use alternative to the FAW blanket. We conducted a single-centre, randomized controlled trial to compare the efficacy of the EasyWarm® self-heating blanket to the Cocoon blanket (Care Essentials, North Geelong, Australia), a conventional FAW blanket, in preventing intraoperative hypothermia. Forty patients undergoing elective surgery under general anaesthesia lasting >1 h were randomized in a 1:1 ratio. Prewarming was not allowed; 39 patients were analysed (19 EasyWarm® group and 20 Cocoon blanket group). There was no statistically significant difference between the two groups with regard to the mean (±standard deviation) final nasopharyngeal temperature (35.89 ± 0.82 °C versus 35.74 ± 0.77 °C; P = 0.72 in the Cocoon and EasyWarm® blanket groups, respectively). Similarly, the difference between average temperatures at 1, 2 and 3 h was not statistically significant. We found the EasyWarm® blanket to be as effective as the Cocoon FAW blanket in preventing intraoperative hypothermia. Due to its ease of use, the EasyWarm® blanket may have an additional benefit in preoperative warming of patients.
  • Article
    Full-text available
    Hip fractures are common orthopedic injuries and are associated with significant morbidity/mortality. Intraoperative normothermia is recommended by national guidelines to minimize additional morbidity/mortality, but limited evidence exists regarding hypothermia's effect on orthopedic patients. The purpose of this study was to determine the incidence of intraoperative hypothermia in patients with operatively treated hip fractures and evaluate its effect on complications and outcomes. Retrospective chart review was performed on clinical records from 1541 consecutive patients who sustained a hip fracture and underwent operative fixation at the authors' institution between January 2005 and October 2013. A total of 1525 patients were included for analysis, excluding those with injuries requiring additional surgical intervention. Patient demographic data, surgery-specific data, postoperative complications, length of stay, and 30-day readmission were recorded. Patients with a mean intraoperative temperature less than 36°C were identified as hypothermic. Statistical analysis with univariate and multivariate logistic regression modeling evaluated associations with hypothermia and effect on complications/outcomes. The incidence of intraoperative hypothermia in operatively treated hip fractures was 17.0%. Hypothermia was associated with an increase in the rate of deep surgical-site infection (odds ratio, 3.30; 95% confidence interval, 1.19-9.14; P=.022). Lower body mass index and increasing age demonstrated increased association with hypothermia (P=.004 and P=.005, respectively). To the authors' knowledge, this is the first and largest study analyzing the effect of intraoperative hypothermia in orthopedic patients. In patients with hip fractures, the study's findings confirm evidence found in other surgical specialties that hypothermia may be associated with an increased risk of deep surgical-site infection and that lower body mass index and increasing age are risk factors for intraoperative hypothermia. [Orthopedics. 201x; xx(x):exx-exx.].
  • Article
    Birth asphyxia, also termed perinatal hypoxia-ischemia, is a modifiable condition as evidenced by improved outcomes of infants ≥36 weeks’ gestation provided hypothermia treatment in randomized trials. Preterm animal models of asphyxia in utero demonstrate that hypothermia can provide short-term neuroprotection for the developing brain, supporting the interest in extending therapeutic hypothermia to preterm infants. This review focuses on the challenge of identifying preterm infants with perinatal asphyxia; the neuropathology of hypoxic-ischemic brain injury across extreme, moderate, and late preterm infants; and patterns of brain injury, use of therapeutic hypothermia, and approach to patient selection for neuroprotective treatments among preterm infants.
  • Article
    Major physiologic alterations following a severe thermal injury disrupt thermal homeostasis and predispose burn patients to hypothermia. An important recommendation in many clinical practice guidelines is to increase the ambient temperature during the care of severely burned patients in the operating room and intensive care unit to mitigate the loss of thermoregulation, prevent hypothermia, and minimize the impact of hypermetabolism. However, the scientific support for this recommendation remains unclear. This review summarizes the current knowledge regarding the pathophysiology and treatment of thermal injury-induced hypermetabolism and hypothermia, with special emphasis on alterations in ambient temperature. Current evidence on the value of increasing ambient temperature during the care of severely burned patients in the operating room or intensive care unit is limited, with minimal human studies investigating physiologic benefit or potential adverse effects.
  • Article
    Clinically relevant influential factors on haemostasis are acidosis, hypothermia, hypocalcaemia and haemodilution, whereas the relevance of poisons is very limited. Each infusion therapy for fluid or volume replacement has potentially negative effects on haemostasis. While the effects of crystalloids (such as physiological saline and plasma-adapted solutions) or human albumin are mainly restricted to the dilutional effect, artificial colloids elicit additional specific effects. Here, dextran produces the strongest, gelatine the least negative effects on haemostasis. Negative haemostatic effects of HES have lost relevance, as becomes obvious when HES 130/0.4 is compared with older preparations.
  • Chapter
    Die physiologische Thermoregulation wird durch alle anästhesiologischen Verfahren beeinträchtigt. Ohne präventive Maßnahmen kommt es daher in der perioperativen Phase sehr häufig zu einer Auskühlung des Patienten. Die pathophysiologischen Konsequenzen der Hypothermie erhöhen das perioperative Risiko. Neben einer veränderten Pharmakokinetik und einem verminderten Patientenkomfort werden eine erhöhte Inzidenz an kardiozirkulatorischen Komplikationen, ein vermehrter Blutverlust und höhere Wundinfektionsraten mit einer perioperativen Hypothermie in Zusammenhang gebracht.
  • Chapter
    Die in den 1980er Jahren geäußerte Hoffnung, den Fremdblutbedarf mit Eigenblutverfahren wesentlich zu reduzieren, hat sich nicht erfüllt. Zum einen sind v. a. präoperative Eigenblutprogramme mit einer hohen Verwurfrate belastet,zum anderen besteht ein offensichtlich steigender Bedarf an Transfusionsblut v. a.für onkologische Patienten, die überwiegend nicht für Eigenblutprogramme in Frage kommen. Unabhängig davon wird von gesundheitspolitischer Seite in der regelhaften Anwendung autologer Transfusionsverfahren ein Beitrag zur nationalen Selbstversorgung mit Blutprodukten gesehen. Neben den juristischen Vorgaben, die eine Aufklärung über die Möglichkeit der Eigenblutspende fordern, sprechen auch medizinische Gründe für Maßnahmen zur Einsparung von Fremdblut. Diese liegen in den Nebenwirkungen wie Infektionen und Antikörperbildung begründet.
  • Chapter
    Unter Narkose kommt es häufig zu einer perioperativen Hypothermie, die durch eine anästhesiebedingte Thermoregulationsstörung in Kombination mit einem voll klimatisierten Operationssaal und daher kühler Umgebungstemperatur entsteht. Perioperative Hypothermie kann zu verschiedenen schwerwiegenden Komplikationen in der postoperativen Phase führen, die nicht unterschätzt werden sollten (Tabelle 24.1).
  • Article
    Blood coagulation is a critical hemostatic process that must be properly regulated to maintain a delicate balance between bleeding and clotting. Disorders of blood coagulation can expose patients to the risk of either bleeding disorders or thrombotic diseases. Coagulation diagnostics using whole blood is very promising for assessing the complexity of the coagulation system and for global measurements of hemostasis. Despite the clinic values that existing whole blood coagulation tests have demonstrated, these systems have significant limitations that diminish their potential for point-of-care applications. Here, recent advancements in device miniaturization using functional soft materials are leveraged to develop a miniaturized clot retraction force assay device termed mHemoRetractoMeter (mHRM). The mHRM is capable of precise measurements of dynamic clot retraction forces in real time using minute amounts of whole blood. To further demonstrate the clinical utility of the mHRM, systematic studies are conducted using the mHRM to examine the effects of assay temperature, treatments of clotting agents, and pro- and anti-coagulant drugs on clot retraction force developments of whole blood samples. The mHRM's low fabrication cost, small size, and consumption of only minute amounts of blood samples make the technology promising as a point-of-care tool for future coagulation monitoring.
  • Article
    The recombinat activated factor VII (rFVIIa Novoseven, Novonordisk, Denmark) has been successfully used in the treatment of hemorrhages in hemophilic patients with inhibitors, in the congenital deficiency of FVII and in Glanzmann's thromboasthenia. Besides, its use has been recommended in non-hemoplilic patients with acquired antibodies against FVIII (acquired hemophilia) and in other disorders of the platelet function as Bernard Soulier Syndrome (SBS). When it is administered at pharmacological doses, it increases the generation of thrombin on the activated platelet, and it may be benefitial in other disorders characterized by profuse bleeding and inadequate generation of thrombin, such as the thrombocytopenias. It has been used in hemorrhages secondary to alterations of the liver function and in severe trauma. Its administration to patients with Rendú Osler Weber's disease and severe bleedings is a new indication, taking into account the activation of coagulation in the specific site of the lesion. It is reported the favorable response of a patient with severe digestive bleeding endangering his life that received rFVII at doses of 90 µg/kg until completing 3 doses in 24 hours. The hemorrhage stopped and its potent hemostatic character in uncontrollable bleedings was confirmed
  • Article
    Introduction Hypothermia is perhaps the most frequent undesirable event in elective surgery. It is estimated that 1 h after surgery has initiated 70–90% of patients will experience hypothermia. In elective surgery, there are several factors leading to temperatures under 34 °C. Hypothermia may increases infections, bleeding and need for transfusion as well as the occurrence of an undesirable effect of discomfort and feared such as cold and postoperative shivering that can lead to cardiac complications due to increased of sympathetic influence. Objectives Review the causes of these low temperatures within intraoperative elective surgery and check if the current alternatives to prevent hypothermia are effective. Methods Review of non-systematic literature in PubMed and Medline was performed. Results Hypothermia is the most common and least diagnosed undesirable event of patients undergoing surgery although it is easy to detect and preventive measures do not present major difficulties in their implementation. Conclusions There are effective measures easy to set up, economical and effective to prevent hypothermia; the most important is the patient warm with hot air under pressure for 1 h and maintenance of air conditioning in the room above 22 °C. We just need to understand these measures and start to implement them.
  • Article
    Full-text available
    Objective Positive end-expiratory pressure (PEEP) causes carotid baroreceptor unloading, which leads to thermoregulatory peripheral vasoconstriction. However, the effects of PEEP on intraoperative thermoregulation in the prone position remain unknown. Methods Thirty-seven patients undergoing spine surgery in the prone position were assigned at random to receive either 10 cmH2O PEEP (Group P) or no PEEP (Group Z). The primary endpoint was core temperature 180 minutes after intubation. Secondary endpoints were delta core temperature (difference in core temperature between 180 minutes and immediately after tracheal intubation), incidence of intraoperative hypothermia (core temperature of <36°C), and peripheral vasoconstriction-related data. Results The median [interquartile range] core temperature 180 minutes after intubation was 36.1°C [35.9°C–36.2°C] and 36.0°C [35.9°C–36.4°C] in Groups Z and P, respectively. The delta core temperature and incidences of intraoperative hypothermia and peripheral vasoconstriction were not significantly different between the two groups. The peripheral vasoconstriction threshold (36.2°C±0.5°C vs. 36.7°C±0.6°C) was lower and the onset of peripheral vasoconstriction (66 [60–129] vs. 38 [28–70] minutes) was slower in Group Z than in Group P. Conclusions Intraoperative PEEP did not reduce the core temperature decrease in the prone position, although it resulted in an earlier onset and higher threshold of peripheral vasoconstriction.
  • Chapter
    Cold exposure resulting in hypothermia can occur following immersion in water, trauma, and exhaustion. Underlying conditions such as hypothyroidism, very young or very old age, cardiac disease or malnutrition may predispose animals to accidental hypothermia at a temperature higher than would otherwise occur in a healthy animal. Other predisposing factors include recreational drugs and ethylene glycol. Cardiac, respiratory, neurological, renal, hematological, acid‐base, and splanchnic perfusion are systems affected to varying degrees based on temperature. Guidelines for core rewarming and fluid therapy, and treatment of frostbite, are cautiously tailored based on degree of hypothermia.
  • Article
    Full-text available
    Thromboelastography (TEG) provides a global evaluation of haemostasis. This diagnostic test is widely used in mammals but has not previously been performed in reptiles, mainly due to the limited availability of taxon-specific reagents. The objective of this pilot study was to establish a protocol to perform TEG in sea turtles. Pooled citrated plasma, stored at −80°C, from four green turtles (Chelonia mydas) was assayed on a TEG 5000. Several initiators were evaluated: kaolin (n=2), RapidTEG (n=2), fresh (n=2) and frozen (n=6) thromboplastin extracted from pooled brain tissue from several chelonian species, human recombinant tissue factor at 1:100 (n=1), Reptilase (n=2), and rabbit thromboplastin (n=1). Both fresh and frozen chelonian thromboplastin were superior in producing quantifiable TEG reaction time compared with all other reagents. These findings are consistent with the lack of an intrinsic pathway in turtles and confirmed a lack of coagulation in the turtle samples in response to mammalian thromboplastin. A TEG protocol was subsequently established for harvested species-specific frozen thromboplastin. The frozen thromboplastin reagent remained stable after one year of storage at −80°C. The developed protocol will be useful as a basis for future studies that aim to understand the pathophysiology of haemostatic disorders in various stranding conditions of sea turtles.
  • Thesis
    INTRODUCTION : Malgré l’amélioration des connaissances et des pratiques, la chirurgie cardiaque reste à haut risque, notamment hémorragique. L’objectif de notre étude est d’identifier les facteurs de risque de saignement en post opératoire précoce après une chirurgie cardiaque réalisée sous CEC. MATERIEL ET METHODES : Nous avons réalisé une étude observationnelle rétrospective monocentrique au CHU de Rouen, du 1er janvier 2016 au 31 juin 2017. Une complication hémorragique était définie par un saignement supérieur à 1.5 mL/kg/heure pendant 6 heures consécutives durant les 24 premières heures post opératoires ou par une reprise chirurgicale lors des 12 premières heures. La recherche des facteurs de risque a été effectuée en calculant l’Odd-Ratio, puis nous avons réalisé une analyse multivariable en régression logistique. RESULTATS : Sur les 1055 patients inclus, 60 ont présenté un saignement important. Les éléments indépendamment associés à un risque moindre de saignement post opératoire faible étaient : l’âge, le BMI, les taux de fibrinogène pré et post opératoire et le TP post opératoire. Ceux indépendamment associés à un saignement post opératoire modéré à sévère étaient la chirurgie associant remplacements valvulaires et pontages, celles des dissections aortiques, la durée de CEC, l’administration de colloïdes en post opératoire et la lactatémie plasmatique post opératoire. CONCLUSION : Différents facteurs ont été identifiés comme ayant une influence sur le saignement en post opératoire précoce de chirurgie cardiaque.
  • Article
    Full-text available
    Background. The avoidance of hypothermia is vital during prolonged and open surgery to improve patient outcomes. Hypothermia is particularly common during orthotopic liver transplantation (OLT) and associated with undesirable physiological effects that can adversely impact on perioperative morbidity. The KanMed WarmCloud (Bromma, Sweden) is a revolutionary, closed-loop, warm-air heating mattress developed to maintain normothermia and prevent pressure sores during major surgery. The clinical effectiveness of the WarmCloud device during OLT is unknown. Therefore, we conducted a randomized controlled trial to determine whether the WarmCloud device reduces hypothermia and prevents pressure injuries compared with the Bair Hugger underbody warming device. Methods. Patients were randomly allocated to receive either the WarmCloud or Bair Hugger warming device. Both groups also received other routine standardized multimodal thermoregulatory strategies. Temperatures were recorded by nasopharyngeal temperature probe at set time points during surgery. The primary endpoint was nasopharyngeal temperature recorded 5 minutes before reperfusion. Secondary endpoints included changes in temperature over the predefined intraoperative time points, number of patients whose nadir temperature was below 35.5°C and the development of pressure injuries during surgery. Results. Twenty-six patients were recruited with 13 patients randomized to each group. One patient from the WarmCloud group was excluded because of a protocol violation. Baseline characteristics were similar. The mean (standard deviation) temperature before reperfusion was 36.0°C (0.7) in the WarmCloud group versus 36.3°C (0.6) in the Bairhugger group (P = 0.25). There were no statistical differences between the groups for any of the secondary endpoints. Conclusions. When combined with standardized multimodal thermoregulatory strategies, the WarmCloud device does not reduce hypothermia compared with the Bair Hugger device in patients undergoing OLT.
  • Article
    Full-text available
    Background: Despite being still invasive and challenging, technical improvement has resulted in broader and more frequent application of extracorporeal membrane oxygenation (ECMO), to prevent hypoxemia and to reduce invasiveness of mechanical ventilation (MV). Heparin-coated ECMO-circuits are currently standard of care, in addition to heparin based anticoagulation (AC) regimen guided by activated clotting time (ACT) or activated partial thromboplastin time (aPTT). Despite these advances, a reliable prediction of hemorrhage is difficult and the risk of hemorrhagic complication remains unfortunately high. We hypothesized, that there are coagulation parameters that are indices for a higher risk of hemorrhage under veno-venous (VV)-ECMO therapy. Methods: Data from 36 patients with severe respiratory failure treated with VV-ECMO at a University Hospital intensive care unit (ICU) were analyzed retrospectively. Patients were separated into two groups based on severity of hemorrhagic complications and transfusion requirements. The following data were collected: demographics, hemodynamic data, coagulation samples, transfusion requirements, change of ECMO-circuit during treatment and adverse effects, including hemorrhage and thrombosis. Results: In this study 74 hemorrhagic events were observed, one third of which were severe. Patients suffering from severe hemorrhage had a lower survival rate on VV-ECMO (43% vs. 91%; P=0.002) and in ICU (36% vs. 86%; P=0.002). SAPS II, factor VII and X were different between mild and severe hemorrhage group. Conclusions: Severe hemorrhage under VV-ECMO is associated with higher mortality. Only factor VII and X differed between groups. Further clinical studies are required to determine the timing of initiation and targets for AC therapies during VV-ECMO.
  • Chapter
    Perioperative thermal disturbances are common and there is considerable evidence that these disturbances are especially frequent in the elderly. The most common perioperative thermal disturbance—hypothermia—is both more likely and more severe in the elderly than in younger patients. Anesthetic drugs impair thermoregulation in all patients, and insufficient thermoregulatory defenses are the primary causes of hypothermia in most patients. Excessive hypothermia in the elderly is mainly due to disturbances in central and efferent thermoregulatory controls. Perioperative hypothermia has long been associated with complications including decreased drug metabolism and postoperative shivering. Even mild hypothermia may worsen perioperative outcomes by augmenting blood loss and transfusion requirement, decreasing resistance to surgical wound infections, and prolonging hospitalization. The elderly are especially susceptible to complications associated with hypothermia because of normal age-related changes in organ function and because many have substantial underlying diseases. However, thermal management for the elderly does not substantially differ from that for younger patients.
  • Article
    Full-text available
    La hipotermia es tal vez el evento indeseable más frecuente en los pacientes que van a cirugía programada. Se considera que una hora después de iniciada la cirugía del 70 al 90% de los pacientes se encuentran hipotérmicos. En cirugía electiva en pacientes sanos hay varios factores que llevan a que nuestros pacientes mantengan cifras de temperatura de 34°C e inclusive menores. El problema está en que la hipotermia aumenta las infecciones, el sangrado y la necesidad de trasfusión, la aparición de un efecto indeseable y temido por el paciente como es el frío y temblor postoperatorio que puede llevar a complicaciones cardiacas debido al aumento del influjo simpático.
  • Article
    Full-text available
    Background: Hypothermia is common in many plastic surgery procedures, but few measures to prevent its occurrence are taken. Objectives: This study evaluated the effect of hypothermia in patients undergoing plastic surgery procedures and the effect of utilizing simple and inexpensive measures to prevent patient hypothermia during surgery. Methods: A randomized controlled clinical trial was performed among 3 groups of patients who underwent body contouring surgery for longer than 3.5 hours. In group 1, no protective measures were taken to prevent hypothermia; in group 2, maneuvers were applied intraoperatively for the duration of the entire surgical procedure; and in group 3, measures were taken preoperatively and intraoperatively. The results were quantified and analyzed through a bivariate analysis, including degree of hypothermia, anesthesia recovery time, time spent in the recovery area, intensity of pain, cold perception, response to opioids, and nausea. Results: There were 122 patients included in the study: 43 in group 1, 39 in group 2, and 40 in group 3. All patients in group 1 had a higher degree of hypothermia, longer recovery time from anesthesia, longer overall recovery time, increased pain, increased feeling of cold, and more nausea. These patients also required a greater amount of opioids compared with the patients in groups 2 and 3. Many of the results were statistically significant. Conclusions: The adoption of simple and inexpensive measures before and during plastic surgery can prevent patient hypothermia during the procedures, leading to a shorter anesthesia recovery time and avoiding the undesirable effects associated with hypothermia. In addition, these measures may have significant economic savings. Level of evidence: 2.
  • Article
    Full-text available
    Abstract Background Chronic subdural hematoma (cSDH) is one of the most common conditions encountered in neurosurgical practice. Recurrence, observed in 5–30% of patients, is a major clinical problem. The temperature of the irrigation fluid used during evacuation of the hematoma might theoretically influence recurrence rates since irrigation fluid at body temperature (37 oC) may beneficially influence coagulation and cSDH solubility when compared to irrigation fluid at room temperature. Should no difference in recurrence rates be observed when comparing irrigation-fluid temperatures, there is no need for warmed fluids during surgery. Our main aim is to investigate the effect of irrigation-fluid temperature on recurrence rates and clinical outcomes after cSDH evacuation using a multicenter randomized controlled trial design. Methods The study will be conducted in three neurosurgical departments with population-based catchment areas using a similar surgical strategy. In total, 600 patients fulfilling the inclusion criteria will randomly be assigned to either intraoperative irrigation with fluid at body temperature or room temperature. The power calculation is based on a retrospective study performed at our department showing a recurrence rate of 5% versus 12% when comparing irrigation fluid at body temperature versus fluid at room temperature (unpublished data). The primary endpoint is recurrence rate of cSDH analyzed at 6 months post treatment. Secondary endpoints are mortality rate, complications and health-related quality of life. Discussion Irrigation-fluid temperature might influence recurrence rates in the evacuation of chronic subdural hematomas. We present a study protocol for a multicenter randomized controlled trial investigating our hypothesis that irrigation fluid at body temperature is superior to room temperature in reducing recurrence rates following evacuation of cSDH. Trials registration ClinicalTrials.gov, ID: NCT02757235 . Registered on 2 May 2016.
  • Article
    Full-text available
    The term “open abdomen” refers to a surgically created defect in the abdominal wall that exposes abdominal viscera. Leaving an abdominal cavity temporarily open has been well described for several indications, including damage control surgery and abdominal compartment syndrome. Although beneficial in certain patients, the act of keeping an abdominal cavity open has physiologic repercussions that must be recognized and managed during postoperative care. This review article describes these issues and provides guidelines for the critical care physician managing a patient with an open abdomen.
  • Article
    The 3 most common reasons for abnormal coagulation of blood in organ donors result from prior medications, consumption or dilution of coagulation factors and platelets during massive transfusion, and disseminated intravascular coagulation. Evaluation and treatment of these conditions are reviewed, and recommendations are provided for ordering appropriate laboratory tests and blood bank products.
  • Article
    Perianesthetic hypothermia is one of the most common complications in veterinary anesthesia, especially in small patients with a large body surface area to mass ratio. During anesthesia, body heat can be lost through 4 mechanisms - radiation, convection, conduction, and evaporation - but anesthetists frequently address only one mechanism at a time. Here we sought to evaluate 3 methods of preventing perianesthetic hypothermia in callimicos (Callimico goeldii). In our experience, these small NHP routinely become hypothermic under even brief inhalant anesthesia. To address multiple routes of heat loss, animals received 1 of 3 treatments: 1) placement of a reflective blanket over the patient to limit radiative heat loss to the surrounding environment; 2) placement of a reflective blanket and use of a heated anesthetic circuit, which warmed the inspired air to 104 °F (40 °C), and 3) placement under the patient of a forced-air warming blanket set at 109.4 °F (43 °C). Sources of radiative heat loss were assessed by using infrared thermography. Each animal was anesthetized with isoflurane and maintained in sternal recumbency in a temperature-controlled room (65 °F; 18.3 °C); esophageal core body temperature was monitored every 5 min for a total of 30 min. The rate of heat loss did not differ between the use of a reflective blanket with or without a heated anesthetic circuit. Animals provided the forced-air warming blanket experienced a slight increase in average body temperature. According to these findings, an underbody warm-air blanket provided the best protection against hypothermia for callimicos in sternal recumbency. Copyright 2017 by the American Association for Laboratory Animal Science.
  • Article
    Full-text available
    Objective: The objectives of this study were to (1) establish the proportion of cerebral palsy (CP) that occurs with a history suggestive of birth asphyxia in children born at 32 to 35 weeks and (2) evaluate their characteristics in comparison with children with CP born at ⩾36 weeks with such a history. Study design: Using the Canadian CP Registry, children born at 32 to 35 weeks of gestation with CP with a history suggestive of birth asphyxia were compared with corresponding ⩾36 weeks of gestation children. Results: Of the 163 children with CP born at 32 to 35 weeks and 738 born at ⩾36 weeks, 26 (16%) and 105 (14%) had a history suggestive of birth asphyxia, respectively. The children born at 32 to 35 weeks had more frequent abruptio placenta (35% vs 12%; odds ratio (OR) 4.1, 95% confidence interval (CI) 1.5 to 11.2), less frequent neonatal seizures (35% vs 72%; OR 0.20, 95% CI 0.08 to 0.52), more frequent white matter injury (47% vs 17%; OR 4.3, 95% CI 1.3 to 14.0), more frequent intraventricular hemorrhage (IVH) (40% vs 6%; OR 11.2, 95% CI 3.4 to 37.4) and more frequent spastic diplegia (24% vs 8%; OR 1.8, 95% CI 1.2 to 12.2) than the corresponding ⩾36 weeks of gestation children. Conclusions: Approximately 1 in 7 children with CP born at 32 to 35 weeks had a history suggestive of birth asphyxia. They had different magnetic resonance imaging patterns of injury from those born at ⩾36 weeks and a higher frequency of IVH. Importantly, when considering hypothermia in preterm neonates with suspected birth asphyxia, prospective surveillance for IVH will be essential.Journal of Perinatology advance online publication, 16 March 2017; doi:10.1038/jp.2017.23.
  • Article
    Background Since the initial design of surgical theatres, the thermal environment of the operating suite itself has been an area of concern and robust discussion. In the 1950s, correspondence in the British Medical Journal discussed the most suitable design for a surgeon's cap to prevent sweat from dripping onto the surgical field. These deliberations stimulated questions about the effects of sweat-provoking environments on the efficiency of the surgical team, not to mention the effects on the patient. Although these benefits translate to implant-based orthopedic surgery, they remain poorly understood and, at times, ignored. Methods A review and synthesis of the body of literature on the topic of maintenance of normothermia was performed. Results Maintenance of normothermia in orthopedic surgery has been proven to have broad implications from bench top to bedside. Normothermia has been shown to impact everything from nitrogen loss and catabolism after hip fracture surgery to infection rates after elective arthroplasty. Conclusion Given both the physiologic impact this has on patients, as well as a change in the medicolegal environment around this topic, a general understanding of these concepts should be invaluable to all surgeons.
  • Chapter
    This chapter is intended to provide the surgeon with an understanding of blood transfusion principles and options as they apply to surgical practice. Issues covered include the risks of allogeneic blood transfusion, alternatives to allogeneic blood, the pathophysiology of anemia in the surgical patient, and the transfusion decision. Evidence is based on a thorough review of the past and current literature.
This research doesn't cite any other publications.