Bone Marrow Transplantation, (1999) 24, 561–566 1999 Stockton Press All rights reserved 0268–3369/99 $15.00 http://www.stockton-press.co.uk/bmt Safety and efficacy of a continuous infusion, patient controlled anti- emetic pump to facilitate outpatient administration of high-dose chemotherapy SP Dix, MK Cord, SJ Howard, JL Coon, RJ Belt and RB Geller Blood and Marrow Transplant Program, Oncology and Hematology Associates and Saint Luke’s Hospital of Kansas City, Kansas City, MO, USA Summary: and colleagues1 described an outpatient BMT care model utilizing intensive clinic support following inpatient admin- We evaluated the combination of diphenhydramine, lor- istration of HDC. This approach facilitated early patient azepam, and dexamethasone delivered as a continuous discharge and significantly decreased the total number of i.v. infusion via an ambulatory infusion pump with days of hospitalization associated with BMT. More patient-activated intermittent dosing (BAD pump) for recently, equipped BMT centers have extended the out- prevention of acute and delayed nausea/vomiting in patient care approach to include administration of HDC in patients receiving high-dose chemotherapy (HDC) for the clinic setting. Success of the total outpatient care peripheral blood progenitor cell (PBPC) mobilization approach is dependent upon the availability of experienced (MOB) or prior to autologous PBPC rescue. The BAD staff and necessary resources as well as implementation of pump was titrated to patient response and tolerance, supportive care strategies designed to minimize morbidity and continued until the patient could tolerate oral anti- in the outpatient setting. emetics. Forty-four patients utilized the BAD pump Despite improvements in supportive care strategies, during 66 chemotherapy courses, 34 (52%) for MOB chemotherapy-induced nausea and vomiting continues to be and 32 (48%) for HDC with autologous PBPC rescue. a side-effect causing significant distress to BMT patients The median number of days on the BAD pump during and one that could limit the use of outpatient care during MOB and HDC was 3 (1–6) and 9 (2–19) days, respect- HDC administration. In a survey evaluating symptom dis- ively. Complete overall or complete emesis control tress in BMT patients receiving high-dose chemotherapy in occurred on 94% of MOB and 89% of HDC treatment the inpatient setting, frequency and severity of nausea were days during chemotherapy administration and 72% and among the symptoms associated with the highest degree of 43%, respectively, following chemotherapy adminis- stress upon discharge from hospital.2 To date, limited data tration. Eighty-three percent of MOB and 55% of HDC are available on anti-emetic regimens that can be safely and treatment days were associated with no nausea. While effectively administered to patients receiving HDC in the on the BAD pump, no patient experienced severe tox- outpatient setting. Thus, the development of such regimens icity or required hospitalization for management of is essential to help facilitate outpatient administration of nausea/vomiting. The BAD pump was safe and effective HDC during BMT. The objective of this study was to in minimizing nausea and vomiting associated with evaluate the safety and efficacy of a combination of three HDC, and thus, eliminated the need for hospitalization anti-emetics with different mechanisms of anti-emetic for management of chemotherapy-induced nausea and action, diphenhydramine (Benadryl, Parke-Davis, Morris vomiting. Plains, NJ, USA), lorazepam (Ativan, Wyeth-Ayerst, Phila- Keywords: high-dose chemotherapy; autologous periph- delphia, PA, USA), and dexamethasone (Decadron, Merck, eral blood progenitor cell transplantation; outpatient BMT; West Point, PA, USA), also called the BAD pump, deliv- anti-emetic therapy ered as a continuous i.v. infusion with patient-controlled i.v. bolus doses, in patients undergoing chemotherapy mob- ilization (MOB) or HDC followed by autologous peripheral blood progenitor cell (PBPC) transplantation in the out- Introduction patient setting. Historically, patients undergoing blood or marrow trans- plantation (BMT) have required prolonged hospitalization Methods for administration of high-dose chemotherapy (HDC) and recovery from regimen-related toxicities. In 1994, Peters Patients were enrolled and evaluated over a 1 year period from October 1996 to October 1997. All patients consented to institutional review board approved treatment protocols Correspondence: SP Dix, Blood and Marrow Transplant Program, Oncology and Hematology Associates of Kansas City, 4320 Wornall including assessments of toxicity and supportive care stra- Road, Suite 220, Kansas City, Missouri 64111, USA tegies. In order to participate, patients were required to have Received 22 May 1998; accepted 28 January 1999 met routine clinical eligibility criteria to undergo autolog- Safety and efficacy of anti-emetic infusion pump SP Dix et al 562 Granisetron 1 mg or BAD pump with basal Ondansetron 32 mg i.v. and = 0.2–0.3 ml/h with 2–3 ml Dexamethasone 10 mg i.v. q 24 h bolus q 15 min lockout on days of i.v. chemotherapy N/V = no N/V = yes no change appropriate use inappropriate use re-evaluate q 24 h and re-educate patient continue BAD pump and caregiver until at least 24 h after PBPC infusion constant N/V intermittent N/V increase basal increase bolus by 25–50% by 25–50% (max = 0.6 ml/h) (max = 6 ml/dose) N/V = no N/V = yes no change individualize or add rescue anti-emetics re-evaluate q 24 h and continue BAD pump until at least 24 h after PBPC infusion and patient able to tolerate oral anti-emetics Additional guidelines: 1 If assessment in outpatient clinic, BMT nurse to make adjustment. If assessment is after hours or on weekend, BMT home health care nurse to make adjustment in conjunction with BMT on-call MD. 2 Options for rescue anti-emetics include: (1) continue to increase basal and/or bolus and titrate to effect; increments must be done in clinic setting; (2) add haloperidol 0.5–1.0 mg p.o. q 6 h; or (3) add prochlorperazine 10 mg p.o.q 6 h Figure 1 Outpatient anti-emetic algorithm: BAD = diphenhydramine 400 mg i.v., lorazepam 16 mg i.v., and dexamethasone 40 mg i.v. in 100 ml D5W non-PVC at 0.2–0.3 ml/h with 2–3 ml bolus q15 min lockout. Doses for each drug as follows: diphenhydramine 0.8–1.2 mg/h with 8–12 mg bolus; lorazepam 0.032–0.048 mg/h with 0.32–0.48 mg bolus; dexamethasone 0.08–0.12 mg/h with 0.8–1.2 mg bolus. ous BMT based on disease status and organ function along Regimens for PBPC mobilization or HDC preparative with the following criteria to undergo outpatient care during regimen were selected based on institutional disease-spe- BMT: (1) the patient must have undergone a psychosocial cific protocols. All chemotherapy doses were initiated in assessment by the BMT social worker with or without the morning in the BMT outpatient clinic. Patients received additional assessment by the BMT-designated clinical psy- standard premedications consisting of a serotonin antagon- chologist or psychiatrist; (2) the patient must have an ist, ondansetron 32 mg i.v. or granisetron 1 mg i.v., plus approved caregiver or caregivers available 24 h a day start- dexamethasone 10 mg i.v. each day beginning 30 min ing at initiation of MOB or HDC; (3) the patient must have before the first dose of chemotherapy. The BAD pump was lodging, either an approved home or hotel, within a 30-min initiated in the afternoon on the first day of high-dose driving radius of the BMT center along with transportation; chemotherapy and administered as outlined in Figure 1. The (4) the patient and caregiver must have attended the BMT BAD pump was prepared by mixing diphenhydramine 400 Caregiver Class and met class objectives prior to initiation mg i.v., lorazepam 16 mg i.v., and dexamethasone 40 mg of MOB or HDC; (5) the patient must have insurance bene- i.v. in a total volume of 100 ml D5W in a non-poly- fits for outpatient care during BMT; and (6) the patient must vinylchloride bag to minimize adsorption. All patients were have signed an informed consent to receive MOB or HDC initiated at a dose of 0.2–0.3 ml/h continuous basal rate followed by autologous PBPCT in the outpatient setting. with a 2–3 ml patient-activated bolus option programmed Safety and efficacy of anti-emetic infusion pump SP Dix et al 563 with a 15-min lockout between boluses. Dosing was based Table 1 Demographics and results on patient weight with patients weighing more than 80 kg initiated at the higher end of the dosing range. The pump Total No. of BAD pump courses 66 was refilled every 48 h or sooner if needed. Dexamethasone No. of mobilization courses 34 (52%) was deleted after a maximum duration of 96 h. The pump (Regimen = cyclophosphamide 4000 mg/m2 i.v. ␮ was continued until at least 24 h after chemotherapy or on day 1, then G-CSF 10 g/kg/d s.c. day 2 or GM-CSF 500 ␮g/d s.c. day 2 to pheresis) PBPC infusion and the patient was able to tolerate oral anti- No. of HDC with autologous PBPCT courses 32 (48%) emetics. The BAD combination was infused via the Abbott Breast CA Provider 6000 ambulatory infusion pump (Abbott Labora- Cyclophosphamide 2000 mg/m2/d days −5, 19 tories, Abbott Park, IL, USA). Patients and caregivers were −4, −3 instructed on battery alarms and changes, and a back-up set Thiotepa 167 mg/m2/d days −5, −4, −3 2 − − − of 9 V batteries were dispensed with each pump. Flumaz- Carboplatin 267 mg/m /d days 5, 4, 3 enil (Romazicon; Roche Laboratories, Nutley, NJ, USA), Multiple myeloma: Melphalan 100 mg/m2/d 6 days −3, −2 the benzodiazepine reversing agent, with necessary supplies NHL: for administration, was also dispensed at the time of Carmustine 300 mg/m2/d day −73 initiation of the pump and kept in the patient’s home or Cytarabine 100 mg/m2 bid days −6, −5, −4, hotel room.