Abstract
We report a 27-year-old hemostatically competent female scheduled for partial hepatectomy. During the operation, she experienced an accidental inferior vena cava tear and suffered acute blood loss. After fluid resuscitation and blood transfusion, she developed hypothermia, with a temperature of 33.8°C, and severe coagulopathy with activated clotting time exceeding 1500 seconds measured using the Hemochron Response system (ITC, Edison, NJ, USA). Despite sufficient blood transfusion and correction of her electrolyte imbalance, the poor hemostasis persisted. After per-forming peritoneal lavage with warm saline, her condition dramatically improved and her hypothermia and severe coagulopathy were reversed.
Keywords
blood coagulation: coagulopathy; hypothermia;
1. Introduction
Acidosis, hypothermia and coagulopathy are identified as a deadly triad.1 These three derangements establish quickly in patients experiencing blood loss, and once they are established, a vicious cycle forms that is difficult to overcome. We report a case with intraoperative massive bleeding resulting in acidosis, hypothermia and coagulopathy. The vicious cycle was broken in this case after aggressive rewarming.
2. Case Report
A 27-year-old female weighing 51 kg with a past history of hepatitis B virus infection for 15 years was admitted for surgical management because of a huge mass in her abdomen. Abdominal computed tomography revealed a hypervascular liver mass of about 22.5 cm in diameter, and she was scheduled for partial hepatectomy. Upon admission, her physical examination was unremarkable except for a palpable mass in the right upper quadrant of the abdomen. She denied any family history of abnormal bleeding and had no symptoms of anemia or signs of bleeding tendency, such as bleeding gums and easy bruising. She was not taking any antiplatelet agents, anticoagulants or other specific medication.
The preoperative laboratory examination showed normal blood tests, except for slightly elevated prothrombin time of 13.72 seconds. The activated partial thromboplastin time was within normal limits. Liver and renal functions were normal. The complete blood count test was also within normal limits. Electrocardiography revealed a normal sinus rhythm. Chest X-ray showed blunting of the right costophrenic angle with signs of pleural effusion.
When the patient arrived in the operating room, her vital signs were stable, except for sinus tachycardia (114 beats/min). Her blood pressure was 136/77 mmHg and body temperature was 37.2ºC. The oxyhemoglobin saturation measured by a pulse oximeter was 100% in room air. General anesthesia was induced with 100 μg of intravenous fentanyl, 20 mg of etomidate and 35 mg of rocuronium. After tracheal intubation, an artificial nose (Gibeck HumidVent Filter Compact S; Kamunting, Perak, Malaysia) was connected to the patient-end of the breathing hose. Anesthesia was maintained by 2−3% sevoflurane in 50% oxygen at a flow rate of 2 L/min. The tidal volume was set at 10 mL/kg and the ventilatory rate was 10 breaths/min. The monitoring items included pulse oximetry, end-tidal carbon dioxide level, electrocardiogram, invasive arterial blood pressure and central venous pressure. Arterial blood was sampled for gas analysis. Fluid was infused at about 300 mL/hr to maintain central venous pressure of 8−10 mmHg and urinary output of about 150 mL/hr. The patient was protected by a water blanket and infusion was given through a fluid warming device to maintain body temperature at 37−37.5ºC.
The surgery continued uneventfully until an accidental tear of the inferior vena cava (IVC), which occurred approximately 8.5 hours after starting the operation (Figure 1). We started resuscitation immediately. We administered 6% hydroxyethyl starch (HES 130/0.4) (Voluven 6% solution; Fresenius Kabi AG, Bad Homburg, Germany) to expand the intravascular volume followed by 12 mg ephedrine and intermittent low-dose epinephrine (20 μg) to maintain hemodynamic status. After establishing a 16- gauge peripheral venous catheter, rapid transfusion of whole blood and packed red blood cells was started. Since the blood loss from the tear was acute and massive, the hemoglobin (Hb) concentration decreased from 11.0 to 7.0 mg/dL at one point. The amount of blood transfusion was adjusted to an acceptable level according to the latest Hb and hematocrit data and the patient’s response to treatment. The total volume of plasma expander (HES) given was 2500 mL. The patient’s urinary output was maintained at 100 mL/hr and her PaO2 was maintained at approximately 350 mmHg under 100% FiO2 during the resuscitation. Nevertheless, the patient’s oral temperature abruptly dropped from 37.4ºC to 34.5ºC during the aggressive fluid and blood transfusion. The tear in the IVC was quickly identified and repaired by the consulting cardiovascular surgeon. Despite the use of a water blanket to keep the patient warm and the fluid and blood being transfused through warming devices, the patient’s temperature continued to drop, reaching 33.8ºC over the ensuing 1 hour. Approximately 90 minutes after the IVC tear, the Hb had increased to 9.8 mg/dL because of the timely transfusion of blood and blood components, including fresh frozen plasma, platelets and cryoprecipitate. The central venous pressure at the time was 12 mmHg, and the rate of transfusion was slowed. However, blood continued to ooze from the surgical field, even though the IVC had been repaired. At this time, the patient’s active clotting time (ACT) was over 1500 seconds, and was followed by acidosis and electrolyte imbalances. The hypocalcemia (0.34 mmol/L) was corrected by aggressive replacement of calcium salts.
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Because the warming measures maintained the patient’s body temperature poorly, we performed peritoneal lavage with warm normal saline approximately 60 minutes after repairing the IVC (Figure 1). This dramatically increased the patient’s body temperature from 33.8ºC to 35.0ºC within 30 minutes.
Before performing the peritoneal lavage and while the patient’s body temperature dropped to 34ºC, the patient became severely metabolically acidotic. Correction of the acidosis was extremely difficult and was only improved after administration of 20 ampoules of 7% sodium bicarbonate (1400 mg/ 20 mL). However, after restoration of the body temperature to 35ºC, the acidosis normalized and plasma pH increased from 7.22 to 7.35, without additional sodium bicarbonate solution administration. Furthermore, the disordered coagulation rapidly reverted to normal. The ACT decreased from over 1500 seconds to 372 seconds, and then to 133 seconds (Figure 1). Hb and hematocrit also steadily increased.
The profuse and diffuse bleeding ceased approximately2.5 hours after the onset of severe bleeding.The operation lasted 14 hours and 25 minutes. Total blood loss was estimated to be 8000 mL, and no sequelae resulted from the massive blood transfusion. The remainder of the patient’s hospital course was unremarkable and the patient was discharged from hospital 1 week later with complete recovery.
3. Discussion
The causes of coagulopathy in patients with severe trauma are usually multifactorial. The interactions among trauma, hypothermia, acidosis and progressive coagulopathy almost always result in severe blood loss.
Our patient developed coagulopathy after severe bleeding caused by a tear in the IVC, which was accompanied by hypothermia and acidosis as a result of the massive transfusion required. The patient’s body temperature decreased markedly because of massive blood loss, rapid infusion of cool plasma expanders, and heat convection via the enlarged open abdomen for exploration and easier IVC repair.2
Bernabei et al reported that there was a close correlation between perioperative temperature and blood loss, independent of the degree of physiologic or anatomic injury.3 Schmied et al found that intraoperative or postoperative blood loss was significantly greater in hypothermic (35.0ºC ± 0.5ºC) patients.4 Thus, it is highly recommended that the lowering body temperature should be restored to physiologic level as quickly as possible. According to the studies by Ferrara et al5 and Cinat et al,6 it is recommended to quickly restore the temperature to ≥ 34ºC or to 36ºC in patients requiring massive transfusion. Despite the presence of normal clotting factors, hypothermia below 33ºC induces a coagulopathy simulating factor-deficiency state, which is functionally equivalent to less than 50% of the normal coagulating activity in normothermic conditions.7 It has been reported that avoidance or correction of hypothermia is essential to prevent or correct coagulopathy in patients receiving massive transfusion.5 Therefore, the appropriate treatment for hypothermia-induced coagulopathy is to perform constitutional rewarming along with the administration of clotting factors.
Temperature-related coagulopathy is caused by impaired activity of clotting factors, platelets and fibrinolysis.8 It has been hypothesized that the kinetics of the enzymes are temperature-dependent, and the series of enzymatic reactions involved in the coagulation cascade could be strongly inhibited by hypothermia.9 In our patient, fluid resuscitation to treat the massive blood loss as a result of the IVC tear led to hypothermia, which was complicated by severe coagulation disorders at a body temperature of 33.8ºC. This exceeded the critical point of 34ºC, at which enzyme activity slows significantly, and resulted in significant changes in platelet activity.10
Although we did not perform laboratory tests to measure the clotting factors during coagulopathy, we performed timely and continuous transfusion of blood and blood components, including 16 units of whole blood, 30 units of packed red blood cells, 18 units of fresh frozen plasma, 24 units of platelets and 12 units of cryoprecipitate. Approximately 90 minutes after the accident, the Hb level was corrected to 9.8 mg/dL, and the blood replacement therapy was considered acceptable. It must be emphasized that we did not administer any clotting factors from the beginning of peritoneal lavage to the time coagulopathy was reversed. Because the total blood loss was around 8000 mL with massive fluid transfusion, the serum coagulation factors might have been diluted to dangerously low levels or lost if no replacement action was taken. To estimate the dilution effects of active transfusion, the serum level of the coagulation factors should be approximately 30% of the normal level when starting peritoneal lavage. However, only 5−20% of factor V and 30% of factor VIII are needed to maintain adequate hemostasis during surgery.11,12 Thus, inadequate levels of clotting factors are unlikely to be the major cause of coagulopathy in our case.
After our patient developed severe hypothermia, she developed metabolic acidosis, which was so intractable that 20 ampoules of 7% sodium bicarbonate solution were insufficient to restore pH. After peritoneal lavage, which raised the body temperature to 35ºC, the acidosis was reversed with only 4 ampoules of 7% sodium bicarbonate solution. Therefore, acceptable body temperature was a key factor involved in the correction of acidosis. The coagulopathy was reversed almost instantly and spontaneously upon correction of body temperature and acidosis. Clearly, body temperature and ACT form a chain of cause and effect. Therefore, temperature is a major factor for ACT normalization and reversal of coagulopathy.
On the other hand, we discovered that adequate replacement of blood components alone was not enough to stop the blood loss in our patient. Impaired hemostasis is often caused by a combination of dilution and consumption of clotting factors, and hyperfibrinolysis. This patient did not have any bleeding tendencies or coagulation disorders. The transfusion of blood components was calculated to stabilize the clotting process. However, even the application of apparently sufficient quantities of fresh frozen plasma, coagulation factors and platelets, hemostasis was not achieved as quickly as desired. One possible reason for the poor transfusion efficacy is that optimal coagulation requires specific preconditions, including acid−base balance, calcium, and body temperature. If these prerequisites are not fulfilled, the application of procoagulants may be in vain because stable clotting does not occur.
The perioperative body temperature should be maintained by controlling the ambient temperature with air-conditioning, covering the exposed surface, warming of the transfused fluids and using an artificial nose in the anesthetic circuit.6,13,14 In our patient, although we applied these techniques, the patient’s body temperature was not well controlled, possibly because the rate of warming was less than the rate of heat loss. Other methods to maintain body temperature include low-flow closed or semiclosed circuit anesthesia, and low-volume fluid resuscitation. Other warming devices, such as radiant warmers and heating lamps, could also be used to maintain the patient’s body temperature.
HES products have potential adverse effects on clot formation, humoral coagulation factors, platelet function, and clot polymerization. These effects have been widely investigated and the extent of the detriment depends on the pharmacokinetic properties of the specific type of HES used, the HES plasma concentrations over time, the presence or absence of plasma accumulation, in vivo molecular weight (MW), and maximum doses.15 According to Kozek-Langenecker et al, rapidly degradable HES solutions of low MW HES (130/0.4) have little effect, if any, on hemostasis.15,16 In terms of proven volume efficacy and the difference in risk for impaired hemostasis, postoperative blood loss and re-operation rate, rapidly degradable (low MW) HES is preferred over slowly degradable (high/medium MW) HES. During resuscitation, we used low MW 6% HES (130/ 0.4) (Voluven; Fresenius Kabi AG) and did not exceed the maximum dose recommended by the manufacturer (50 mL/kg/day). The abnormal bleeding was resolved within 1.5 hours, which was far shorter than the elimination half-life, 12 hours, of 6% HES (130/ 0.4). Therefore, the coagulopathy seemed to be unrelated to the 6% HES (130/0.4) in our patient.
Peritoneal lavage rapidly corrected the hypothermia and comprised an important turning point in the reversal of coagulopathy, shortened the operation time, limited the amount of blood transfusion required, and reduced the risk of morbidity and mortality in our case. Anesthesiologists should be aware that even with a single abnormal physical parameter (in this example, body temperature), aggressive correction of hypothermia could change a potential intraoperative tragedy into a very different scenario. Close cooperation between the surgeon and anesthesiologist to avoid intraoperative complications should be emphasized.