Initial Labwork:
Dancer's labwork showed a low platelet value of 33,000 (range 200,000-500,000) and prolonged clotting values for prothrombin time (PT) and partial thromboplastin time (PTT). Her initial PCV/TS = 54%/7.2. All else was within normal limits except mildy low potassium and an elevated BUN of 39 (5-25) and ALT of 359 (10-150).
Initial Stabilization:
Immediately, an intravenous catheter was placed while Dancer received flow-by oxygen. Active cooling efforts were started simultaneously. These included placing Dancer on a metal table, saturating the trunk of her body with room temperature water, placing a fan to blow directly onto her, and administering intravenous fluids. Dancer received a crystalloid bolus of 22mL/kg of Normosol R and then was placed on intravenous fluids at 60ml/kg/day awaiting thawing of fresh frozen plasma (FFP). Her temperature dropped to 103.5F within 30 minutes of presentation. The fan was turned off and she was no longer saturated with water. Once her temperature dropped to 102.5F, she was dried off and her temperature monitored every 5 minutes until stabilization.
ICU Treatment:
The FFP transfusion of 240mL (double unit) was started within 90 minutes of presentation. For Dancer's body weight, this was approximately 9mL/kg administered over 3 hours. She continued to produce large quantities of bloody, watery diarrhea during the transfusion. Unfortunately, she developed petechiations on the skin of her abdomen (a sign of low platelets and/or clotting deficiency) and her clotting parameters did not return to normal ranges at the 3-hour post-transfusion recheck. Over the first 24 hours of being hospitalized at The COVE, Dancer required 3 FFP transfusions for a total of 30mL/kg and would receive 2 more FFP transfusions before her clotting values normalized for a grand total of 45mL/kg. Dancer was refractory to the aggressive supplementation of plasma because her body was going into septic shock and organ failure before our eyes. Her coagulation system was in high gear continually activating the newly transfused clotting factors. Her kidney and liver values climbed while her blood sugar dropped to dangerously low levels. She developed gastro-intestinal ileus and started regurgitating bloody fluid. On abdominal ultrasound, we discovered that her stomach was markedly distended with fluid with no sign of peristalsis. Her red blood cell level dropped due to gastrointestinal bleeding necessitating a packed red blood cell transfusion on Day 3. During her stay, medications included intravenous fluids with dextrose supplementation, broad-spectrum antibiotics (Unasyn, enrofloxacin, and metronidazole), pantoprazole, sucralfate, maropitant, low-dose erythromycin and metoclopramide
Dancer was extremely lucky and a tough girl. By the evening of Day 3, she was eating and drinking water well. She had been weaned off her fluids and onto oral medications. She was slowly regaining her strength and trying to play with the staff. Despite her energetic demeanor, bloodwork indicated that her bone marrow had been badly damaged. She had a non-regenerative pancytopenia; her hematocrit remained at 19% with an absolute reticulocyte count of 5800 (range <60,000), platelet count of 58,000 /uL, and neutrophil count of 120/uL. CBCs were monitored every 48 hours, showing minimal improvement in her non-regenerative pancytopenia. She was cautiously sent home on the 10th day of her hospitalization on Clavamox, enrofloxacin, metronidazole, sucralfate, and omeprazole with instructions to keep quiet, monitor appetite/energy, and recheck CBC in 5-7 days.
Outcome:
Dancer's petechiations and areas of ecchymoses healed. She continued to eat well and the owner had a difficult time keeping her "quiet" due to her high energy level as a young Lab. She returned for a recheck examination and blood work on the 16th day after the initial heat stroke episode. Labwork was within normal limits with a reticulocytosis of 175,000 confirming that her bone marrow was functional. She is currently doing very well and is kept indoors during the heat of the summer.
Discussion:
Exertional heat stroke is not uncommon in our hot and humid summer climate. It can happen in as short has 30 minutes if dogs are not given time to rest, ample shade, and water. Risk factors include lack of acclimation to change in climate, brachycephalic airway syndrome, laryngeal paralysis, collapsing trachea, and obesity. In Dancer's case, her body had not been exposed to the heat and humidity of a Virginia summer before.
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The mainstay of therapy is active cooling, restoration of circulating blood volume, and treatment of coagulopathy, organ dysfunction, and/or sepsis. Anti-pyretic medications such as NSAIDs and corticosteroids are ineffective and contraindicated as this type of hyperthermia is secondary to ineffective cooling and not endogenous pyrogens. These drugs can worsen GI ulceration and potentiate renal and hepatic injury.
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Direct thermal injury and hypoperfusion secondary to hypovolemic shock can lead to the complications seen with heat stroke. Thermal injury damages every cell of the body with the most clinically significant being enterocytes of the GI tract, hepatocytes, renal tubular cells, neurons, and the endothelium. A temperature as low as 105.8F can result in cellular dysfunction, however, protein denaturation typically does not occur until temperatures reach 109F. There is interplay between this systemic inflammation and activation, and subsequent exhaustion, of the coagulation system including platelets and clotting factors. Additionally at these high temperatures clotting factors, being proteins, are inactivated and the liver, which produces new clotting factors, is damaged and may have reduced function. The bone marrow does not escape this thermal injury and platelets and white and red blood cell precursors can be destroyed. Therefore, patients experiencing heat stroke may develop petechiations, ecchymoses, and bleeding into cavities and lumens such as the GI tract. Bacterial translocation across the damaged GI tract can result in hypoglycemia and sepsis.
Therapy should be directed at rapid, safe cooling including intravenous fluids, saturation of the trunk with room temperature fluids, and a fan placement for convective cooling. Additional treatments include fluid therapy, broad-spectrum antibiotics, gastro-protectants, and blood product administration, as needed. Prognosis is multi-factorial and based on length of exposure, highest temperature reached, comorbid conditions, and complications such as DIC, renal failure, and coagulopathy. Most patients are given a guarded prognosis, however, those who present in a coma or hypothermic (after the heat stroke event) have a grave prognosis. Blood smear analysis is a useful prognostic tool and can guide discussion with owners as a 2009 research paper showed that finding 18 or more nRBCs/100 leukocytes predicted death in heat stroke patients (J Vet Intern Med 2009; 23: 544-551).
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HELPFUL HINTS ON GASTRIC EMPTYING MEDICATIONS
Gastric stasis is not an uncommon sequella of shock. Resultant regurgitation will prolong hospitalization time, decrease time to enteral feeding tolerance, and predispose to aspiration pneumonia. Metoclopramide (Reglan) is the most common promotility medication used in veterinary medicine. It is a dopaminergic (D2) receptor antagonist with mixed 5-HT3 antagonist and 5-HT4 agonist effects. It is a centrally acting antiemetic and increases gastric motility via muscarinic receptors.
Erythromycin is a macrolide antibiotic which has recently been utilized in people for its prokinetic gastric effects. At low doses (1-3mg/kg IV/PO q 8), it is a motilin receptor agonist that stimulates gastric contractions by triggering myoelectric migrating complexes. When paired with metoclopramide, the effects are superior to either drug alone. In my experience, erythromycin works well in dogs and can markedly reduce hospitalization time in patient's with refractory gastroparesis.
For those interested the below articles compare at the use of erythromycin and metoclopramide in feeding intolerance (mostly human research):
- Nguyen NQ, Chapman MJ, Fraser RJ, Bryant LK, Holloway RH. Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness. Crit Care Med. 2007 Feb;35(2):483-9.
- Nguyen NQ, Chapman M, Fraser R et al. Prokinetic therapy for feed intolerance in critical illness: one drug or two? Crit Care Med 2007;35:2561-57.
- Robert MacLaren, Tyree H Kiser, Douglas N Fish, Paul E Wischmeyer. Erythromycin vs metoclopramide for facilitating gastric emptying and tolerance to intragastric nutrition in critically ill patients. JPEN Journal of parenteral and enteral nutrition 2008. Volume: 32, Issue: 4, Pages: 412-419.
- Carlson RG, Hocking MP, Courington KR, Sninsky CA, Vogel SB. Erythromycin enhances delayed gastric emptying in dogs after Roux-Y antrectomy. Am J Surg. 1991 Jan;161(1):31-4.
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Severe heat stroke causes direct thermal injury to the body tissues and the endothelium leading to activation of the coagulation cascade and subsequent consumption of platelets and coagulation factors. If left untreated, disseminated intravascular coagulation can occur resulting in organ dysfunction, bleeding, and a grave prognosis. Transfusion of clotting factors via fresh frozen plasma (FFP) can be performed to deliver replacement factors to prevent bleeding. A unit of FFP contains coagulation proteins such as Factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand's Factor (vWF), fibrinogen and anticoagulants such as antithrombin, protein C, and protein S and fibrinolytic proteins such as plasminogen, antiplasmin, plasminogen activator inhibitor-1, however does not contain platelets. Administration of fresh whole blood will replace a small number of platelets, however, the blood must be transfused within 6 hours of being drawn and kept at room temperature. There is controversy regarding viability of transfused platelets as they become activated and expended easily. Thankfully, in my experience, heat stroke patients rarely require platelet replacement. The dosage of FFP is 10-20mL/kg with more severe heat stroke patients requiring additionally transfusions. Rarely transfusion reactions can occur so patients are monitored closely for any allergic or anaphylactic reactions.
For questions regarding heat stroke or any other ERCC situation, please do not hesitate to contact Shelley Smith, DVM, DACVECC at 757.935.9111 or
[email protected].
