JOURNAL OF PALLIATIVE MEDICINE Volume 19, Number 3, 2016 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2015.0453
Use of Propofol To Manage Nonmalignant Intractable Nausea and Vomiting: A Case Study Leslie Hunter-Johnson, MS, RN-BC, CCRN, CNRN, CHPN1 and Warren L. Wheeler, MD, HMDC2
Dear Editor: Case I
A 24-year-old woman was admitted to the hospital for scheduled colostomy and ileostomy reversal with exploratory laparotomy and lysis of adhesions. She also had refractory nausea and vomiting for which the palliative care team was consulted. Her past surgical history was complex. She originally presented to the emergency department with severe abdominal pain, constipation, and sepsis due to multiple bowel perforations. A partial small bowel resection was performed. The postoperative course was complicated by ischemia and recurrent perforation requiring further bowel resections. She was discharged in a debilitated state with a colostomy, ileostomy, tracheostomy, percutaneous gastrostomy tube (PEG), and chronic ventilation. Several months later she was readmitted for endocarditis and mitral valve regurgitation treated with antibiotics and mitral valve replacement. Radiographic evaluation showed no obstruction. Laboratory evaluation revealed an elevated C-reactive protein 16.57 (normal range 0.30–5.00 mmols/L), and decreased haptoglobin 1.0 (normal range 40–240). Genetic testing revealed two mutations of methylenetetrahydrofolate-reductase (MTHFR).1,2 She was heterozygous for both MTHFR C677T and A12298C.2,3 The cause of her nausea and vomiting was thought to be multifactorial. The following medications were ineffective at managing the symptom: (1) H1 antagonist diphenhydramine (Benadryl) and hydroxyzine; (2) anticholinergics glycopyrrolate (Robinul), scopolamine, and atropine; (3) postsynaptic dopamine receptor antagonists haloperidol (Haldol), prochlorperazine (Compazine), promethazine (Phenergan), respiridone (Risperdal), and quetiapine (Seroquel); (4) delta-9 tetrahydrocannabinol (Marinol); (5) HT-3 serotoninreceptor antagonists ondansetron (Zofran and granisetron (Kytril); (5) prokinetic agents metoclopramide (Reglan) mirtazapine and erythromycin; (6) corticosteroid prednisone; and (7) benzodiazepines lorazepam (Ativan), diazepam (Valium), and midazolam (Versed). Regardless of what was prescribed, the patient had persistent nausea and vomiting. The
1 2
diagnosis of psychogenic nausea and vomiting was entertained. However, supportive psychotherapy and selective-serotonin reuptake inhibitors resulted in no improvement. Propofol at 3 mcg/kg/min was initiated and completely relieved the nausea and vomiting without an adverse effect on level of consciousness. Within four hours the patient asked to sit up in the bedside chair, painted her nails, and applied make-up. Later that same day she asked for a few potato chips. The nurse brought in three Doritos chips. A few minutes later she called the nurse and asked for more and proceeded to consume the entire bag of the chips. Her demeanor improved over the next few days, as did her activity. On day three, the dose of propofol was reduced by 50% and completely discontinued on day five. She was observed over the next two days and was discharged home with her family. Case 2
A 24-year-old man was admitted to the hospital with biopsy-proven cerebritis and severe nausea and vomiting that was refractory to a variety of treatments like Case 1. When propofol at 3 mcg/kg/min was initiated, he sat up and asked for a cheeseburger within minutes of the initiation of the infusion. Discussion
Propofol has been reported to reduce postoperative nausea and vomiting as well as being an antiemetic in palliative cancer care.4 As a GABAA receptor agonist, it reduces the concentration of serotonin and 5-hydroxyindoleacetic acid in the lateral wall of the fourth ventricle; the area postrema.4,5 Our hospital policy permits propofol for ICU patients who are intubated for purposes of sedation. It is also used for procedural sedation and prevents postoperative nausea and vomiting. Hospital policy did not permit administration as described here. In these two cases, several departments had to approve of the administration for off-label use. Discussions with the surgeon, pharmacy, nursing director, risk management, and the chief medical officer occurred and provided approval with the caveat that the patient be monitored with oximetry and capnography.
Division of Palliative Medicine, Sunrise Hospital and Medical Center, Las Vegas, Nevada. Division of Palliative Medicine, Elaine Wynn Palliative Care Program, Nathan Adelson Hospice, Las Vegas, Nevada.
252
LETTERS TO THE EDITOR Conclusion
We think these cases suggest propofol be a pharmacological approach to management of refractory nausea and vomiting. Until further data emerge, we will continue to prescribe low dose IV propofol at 3 mcg/kg/min as a continuous infusion for 72–96 hours. We will titrate if needed to control symptoms, avoiding sedative dosing. The patient at low-dose propofol does not require intubation or a monitored setting, but for safety prevention should be closely monitored with pulse oximetry and capnography. We advocate continued treatment after symptoms of nausea or vomiting are controlled for at least 72–96 hours. Then reduce the propofol dose by 50%, continue another 24 hours, then discontinue. Our rationale for continuing propofol for three to four days after nausea and vomiting are controlled is to allow the physiology of the body to ‘‘reset’’ itself and for the brain to ‘‘learn’’ not to be nauseated. Literature search shows safety in nonventilated cancer patients receiving propofol doses at 0.5–6.0 mg/kg/hour (mean dose of 0.90–2.13 mg/kg/hour).4.6 References
1. Vargas EA, Sturm AC, Misita CP, Moll S: Homocysteine and MTHFR mutations relation to thrombosis and coronary artery disease. Circulation 2005;111:289–293.
253
2. Leclerc D, Sibani S, Rozen, R: Molecular biology of methylenetetrahydrofolate reductase (MTHFR) and overview of mutations/polymorphisms. In: Madame Curie Bioscience Database. Austin, TX: Landes Bioscience, 2000. 3. Hickey SE, Curry CJ, Toriello, HV: ACMG practice guideline: Lack of evidence for MTHFR polymorphism testing. Genet Med 2013;15:153–156. 4. Lungstro¨m S., Zachrission U, Fu¨rstm CJ: When nothing helps: Propofol as sedative and antiemetic in palliative cancer care. J Pain Symptom Manage 2005;30:570–577. 5. Golembiewski J, Chernin E, Chopra T: Prevention and treatment of postoperative nausea and vomiting. Am J Health Syst Pharm 2005:15;62:1247–1260. 6. Moos DD, South K: Propofol. Gastrointest Nurs 2006;29: 176–178.
Address correspondence to: Leslie Hunter-Johnson, MSN, RN-BC, CCRN, CNRN, CHPN Sunrise Hospital and Medical Center Division of Palliative Medicine 3186 South Maryland Parkway Las Vegas, NV 89109 E-mail: [email protected]
Use of Propofol To Manage Nonmalignant Intractable Nausea and Vomiting: A Case Study Leslie Hunter-Johnson, MS, RN-BC, CCRN, CNRN, CHPN1 and Warren L. Wheeler, MD, HMDC2
Dear Editor: Case I
A 24-year-old woman was admitted to the hospital for scheduled colostomy and ileostomy reversal with exploratory laparotomy and lysis of adhesions. She also had refractory nausea and vomiting for which the palliative care team was consulted. Her past surgical history was complex. She originally presented to the emergency department with severe abdominal pain, constipation, and sepsis due to multiple bowel perforations. A partial small bowel resection was performed. The postoperative course was complicated by ischemia and recurrent perforation requiring further bowel resections. She was discharged in a debilitated state with a colostomy, ileostomy, tracheostomy, percutaneous gastrostomy tube (PEG), and chronic ventilation. Several months later she was readmitted for endocarditis and mitral valve regurgitation treated with antibiotics and mitral valve replacement. Radiographic evaluation showed no obstruction. Laboratory evaluation revealed an elevated C-reactive protein 16.57 (normal range 0.30–5.00 mmols/L), and decreased haptoglobin 1.0 (normal range 40–240). Genetic testing revealed two mutations of methylenetetrahydrofolate-reductase (MTHFR).1,2 She was heterozygous for both MTHFR C677T and A12298C.2,3 The cause of her nausea and vomiting was thought to be multifactorial. The following medications were ineffective at managing the symptom: (1) H1 antagonist diphenhydramine (Benadryl) and hydroxyzine; (2) anticholinergics glycopyrrolate (Robinul), scopolamine, and atropine; (3) postsynaptic dopamine receptor antagonists haloperidol (Haldol), prochlorperazine (Compazine), promethazine (Phenergan), respiridone (Risperdal), and quetiapine (Seroquel); (4) delta-9 tetrahydrocannabinol (Marinol); (5) HT-3 serotoninreceptor antagonists ondansetron (Zofran and granisetron (Kytril); (5) prokinetic agents metoclopramide (Reglan) mirtazapine and erythromycin; (6) corticosteroid prednisone; and (7) benzodiazepines lorazepam (Ativan), diazepam (Valium), and midazolam (Versed). Regardless of what was prescribed, the patient had persistent nausea and vomiting. The
1 2
diagnosis of psychogenic nausea and vomiting was entertained. However, supportive psychotherapy and selective-serotonin reuptake inhibitors resulted in no improvement. Propofol at 3 mcg/kg/min was initiated and completely relieved the nausea and vomiting without an adverse effect on level of consciousness. Within four hours the patient asked to sit up in the bedside chair, painted her nails, and applied make-up. Later that same day she asked for a few potato chips. The nurse brought in three Doritos chips. A few minutes later she called the nurse and asked for more and proceeded to consume the entire bag of the chips. Her demeanor improved over the next few days, as did her activity. On day three, the dose of propofol was reduced by 50% and completely discontinued on day five. She was observed over the next two days and was discharged home with her family. Case 2
A 24-year-old man was admitted to the hospital with biopsy-proven cerebritis and severe nausea and vomiting that was refractory to a variety of treatments like Case 1. When propofol at 3 mcg/kg/min was initiated, he sat up and asked for a cheeseburger within minutes of the initiation of the infusion. Discussion
Propofol has been reported to reduce postoperative nausea and vomiting as well as being an antiemetic in palliative cancer care.4 As a GABAA receptor agonist, it reduces the concentration of serotonin and 5-hydroxyindoleacetic acid in the lateral wall of the fourth ventricle; the area postrema.4,5 Our hospital policy permits propofol for ICU patients who are intubated for purposes of sedation. It is also used for procedural sedation and prevents postoperative nausea and vomiting. Hospital policy did not permit administration as described here. In these two cases, several departments had to approve of the administration for off-label use. Discussions with the surgeon, pharmacy, nursing director, risk management, and the chief medical officer occurred and provided approval with the caveat that the patient be monitored with oximetry and capnography.
Division of Palliative Medicine, Sunrise Hospital and Medical Center, Las Vegas, Nevada. Division of Palliative Medicine, Elaine Wynn Palliative Care Program, Nathan Adelson Hospice, Las Vegas, Nevada.
252
LETTERS TO THE EDITOR Conclusion
We think these cases suggest propofol be a pharmacological approach to management of refractory nausea and vomiting. Until further data emerge, we will continue to prescribe low dose IV propofol at 3 mcg/kg/min as a continuous infusion for 72–96 hours. We will titrate if needed to control symptoms, avoiding sedative dosing. The patient at low-dose propofol does not require intubation or a monitored setting, but for safety prevention should be closely monitored with pulse oximetry and capnography. We advocate continued treatment after symptoms of nausea or vomiting are controlled for at least 72–96 hours. Then reduce the propofol dose by 50%, continue another 24 hours, then discontinue. Our rationale for continuing propofol for three to four days after nausea and vomiting are controlled is to allow the physiology of the body to ‘‘reset’’ itself and for the brain to ‘‘learn’’ not to be nauseated. Literature search shows safety in nonventilated cancer patients receiving propofol doses at 0.5–6.0 mg/kg/hour (mean dose of 0.90–2.13 mg/kg/hour).4.6 References
1. Vargas EA, Sturm AC, Misita CP, Moll S: Homocysteine and MTHFR mutations relation to thrombosis and coronary artery disease. Circulation 2005;111:289–293.
253
2. Leclerc D, Sibani S, Rozen, R: Molecular biology of methylenetetrahydrofolate reductase (MTHFR) and overview of mutations/polymorphisms. In: Madame Curie Bioscience Database. Austin, TX: Landes Bioscience, 2000. 3. Hickey SE, Curry CJ, Toriello, HV: ACMG practice guideline: Lack of evidence for MTHFR polymorphism testing. Genet Med 2013;15:153–156. 4. Lungstro¨m S., Zachrission U, Fu¨rstm CJ: When nothing helps: Propofol as sedative and antiemetic in palliative cancer care. J Pain Symptom Manage 2005;30:570–577. 5. Golembiewski J, Chernin E, Chopra T: Prevention and treatment of postoperative nausea and vomiting. Am J Health Syst Pharm 2005:15;62:1247–1260. 6. Moos DD, South K: Propofol. Gastrointest Nurs 2006;29: 176–178.
Address correspondence to: Leslie Hunter-Johnson, MSN, RN-BC, CCRN, CNRN, CHPN Sunrise Hospital and Medical Center Division of Palliative Medicine 3186 South Maryland Parkway Las Vegas, NV 89109 E-mail: [email protected]
