Marieberta Vidal

Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial

Importance The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. Objective To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. Design, Setting, and Participants Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. Interventions Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. Main Outcomes and Measures The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, −5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. Results Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (−4.1 points) than placebo + haloperidol (−2.3 points) (mean difference, −1.9 points [95% CI, −2.8 to −0.9]; P < .001). The lorazepam + haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, −1.0 mg [95% CI, −2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol group vs 30% for the placebo + haloperidol group; mean difference, 47% [95% CI, 17% to 71%], P = .005). No significant between-group differences were found in delirium-related distress and survival. The most common adverse effect was hypokinesia (3 patients in the lorazepam + haloperidol group [19%] and 4 patients in the placebo + haloperidol group [27%]). Conclusions and Relevance In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. Further research is needed to assess generalizability and adverse effects. Trial Registration clinicaltrials.gov Identifier: NCT01949662

The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients

Transdermal fentanyl (TDF) is 1 of the most common opioids prescribed to patients with cancer. However, the accurate opioid rotation ratio (ORR) from other opioids to TDF is unknown, and various currently used methods result in wide variation of the ORR. The objective of this study was to determine the ORR of the oral morphine equivalent daily dose (MEDD) to the TDF dose when correcting for the MEDD of breakthrough opioids (the net MEDD) in cancer outpatients.

The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients

PURPOSE Cancer pain management guidelines recommend initial treatment with intermediate-strength analgesics such as hydrocodone and subsequent escalation to stronger opioids such as morphine. There are no published studies on the process of opioid rotation (OR) from hydrocodone to strong opioids in cancer patients. Our aim was to determine the opioid rotation ratio (ORR) of hydrocodone to morphine equivalent daily dose (MEDD) in cancer outpatients. PATIENTS AND METHODS We reviewed the records of consecutive patient visits at our supportive care center in 2011-2012 for OR from hydrocodone to stronger opioids. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and MEDD were collected from patients who returned for follow-up within 6 weeks. Linear regression analysis was used to estimate the ORR between hydrocodone and MEDD. Successful OR was defined as 2-point or 30% reduction in the pain score and continuation of the new opioid at follow-up. RESULTS Overall, 170 patients underwent OR from hydrocodone to stronger opioid. The median age was 59 years, and 81% had advanced cancer. The median time between OR and follow-up was 21 days. We found 53% had a successful OR with significant improvement in the ESAS pain and symptom distress scores. In 100 patients with complete OR and no worsening of pain at follow-up, the median ORR from hydrocodone to MEDD was 1.5 (quintiles 1-3: 0.9-2). The ORR was associated with hydrocodone dose (r = -.52; p < .0001) and was lower in patients receiving ≥40 mg of hydrocodone per day (p < .0001). The median ORR of hydrocodone to morphine was 1.5 (n = 44) and hydrocodone to oxycodone was 0.9 (n = 24). CONCLUSION The median ORR from hydrocodone to MEDD was 1.5 and varied according to hydrocodone dose.

The Frequency and Factors Associated With the Use of a Dedicated Supportive Care Center Telephone Triaging Program in Patients With Advanced Cancer at a Comprehensive Cancer Center

CONTEXT There is limited literature on characteristics of telephone triage programs and the nature of interventions in palliative care. OBJECTIVES Our aim was to determine frequency and type of care provided by a Supportive Care Center Telephone Triaging Program (SCCTP) in advanced cancer patients (ACPs). METHODS Electronic medical records were reviewed of 400 consecutive ACPs referred to palliative care at a comprehensive cancer center and given access to the SCCTP: 200 from the outpatient (OP) supportive care center and 200 from inpatient (IP) palliative care given access after discharge. We reviewed call frequency, type, reason, and outcomes including pain and other symptoms (Edmonton Symptom Assessment Scale and Memorial Delirium Assessment Scale [MDAS]) associated with utilization of the SCCTP. RESULTS A total of 375 patients were evaluable. One hundred fifteen of 400 patients (29%) used the SCCTP: 96 OPs (83%) used the SCCTP vs. only 19 IPs (17%) (P < 0.001). The most common reasons for calls were pain (24%), pain medication refills (24%), and counseling (12%). For 115 phone calls, 43% (145 of 340) of recommendations were regarding care at home and 56% were regarding opioids. Patients who used the SCCTP had worse pain (P = 0.006), fatigue (P = 0.045), depression (P = 0.041), and well-being (P = 0.015) and better MDAS scores (P = 0.014) compared with nonusers. OPs had a higher prevalence of symptom distress (P = 0.013), depression (P < 0.001), anxiety (P < 0.01), and insomnia scores (P = 0.001); MDAS scores were significantly higher in IPs (P < 0.001). CONCLUSION In this study, we found that overall utilization of the SCCTP by ACPs referred to palliative care was relatively low at 28.7%. The use of the SCCTP was particularly poor among the IPs on discharge. Patients who used SCCTP had worse pain, fatigue, depression, and well-being scores and better delirium scores.

Impact of a Palliative Care Checklist on Clinical Documentation

PURPOSE Checklists are used in many different settings for the purpose of standardization and reduction of preventable errors in practice. Our group sought to determine whether a palliative care checklist (PCC) would improve the clinical documentation of key patient information. METHODS An initial review of 110 randomly selected medical records dictated by 10 physicians was performed. The authors identified portions of the dictated medical records that were included regularly, as well as those that were frequently missed. A PCC was drafted after final approval was obtained from the 13 faculty members. Dictations from 13 clinical faculties in the supportive care center were reviewed. A χ(2) test or Fishers exact test was applied to assess the difference in overall checked rates before and after checklist use. A paired t test was used to examine the difference in the average complete rate and checked rates before and after checklist use. RESULTS There were improvements in the documentation before and after the checklist for scores on the Cut-down, Annoyed, Guilty, Eye-opener questionnaire for alcoholism (79% v 94%; P ≤ .0001), psychosocial history (69% v 95%; P ≤ .0001), Eastern Cooperative Oncology Group performance status (38% v 81%; P ≤ .0001), advance care planning (28% v 41%; P = .0008), and overall (78% v 95%; P ≤ .0001). There was no significant improvement in the documentation for opioid-induced neurotoxicity (37% v 37%; P = .9492) or the Edmonton Symptom Assessment Scale (98% v 99%; P = .4511). CONCLUSION Our study showed that the use of a PCC improved the quality of the documentation of a patient visit in an outpatient clinical setting.

A prospective study: Hypodermoclysis performed by caregivers in the home setting.

128 Background: Decreased oral intake is very common at the end of life. Dehydration can aggravate symptoms like fatigue, myoclonus, and confusion. Intravenous (iv) hydration at home can be uncomfortable and expensive. Hypodermoclysis (HDC) is a comfortable and inexpensive but rarely used way to provide hydration at the end of life in the home setting. The purpose of this study was to evaluate a program of HDC at home by the caregivers. METHODS All caregivers underwent a 45 minute training session on HDC administration and assessment of infusion site delivered by a specially trained nurse. Caregivers received daily calls and on site evaluation on day 8. RESULTS A total of 21 patient/caregivers dyads were admitted to this preliminary study: 10 (47%) female patients and 16 (76%) female caregivers. All patients had advanced cancer receiving hospice care at home. All caregivers who received training were able to start the infusion. Side effects were minimal with 1 (5%) care of the needle difficulty and leakage. CONCLUSIONS This preliminary study suggests that subcutaneous hydration can be administered by caregivers at home with minimal burden. It can be easily done by just gravity or weight. It will avoid the use of expensive iv pump devices or need of special technical support. [Table: see text].

Impact of a dedicated supportive care center telephone triaging program (SCCTP) for patients with advanced cancer.

54 Background: Due to high symptom burden in advanced cancer patients, ongoing symptom management for outpatient palliative care patients is vital. More patients are receiving outpatient care; Yet, most palliative care patients receive less than 2 follow ups. Nurse telephone care can improve quality of life in these patients. Our aim was to determine frequency and care provided by Supportive Care Center Telephone Program (SCCTP) in advanced cancer patients. METHODS 400 consecutive patients who utilized palliative care service, 200 from outpatient Supportive Care Center (SCC) and 200 from inpatient Palliative Care (IPC), were followed for 6 months starting 3/2012 to examine call frequency and reason and outcomes including pain and other symptoms [Edmonton Symptom Assessment Scale (ESAS) and Memorial Delirium Assessment Scale (MDAS)] associated with utilization of SCCTP. We also examined the effect of SCCTP interventions on pain, ESAS and counseling needs. RESULTS 375 patients were evaluable. Median age 59 years, 53% female, 70% white. Most frequent cancer type were gastrointestinal (20%, p < 0.0001) for IPC and thoracic (23%, p <0.0001) for SCC. SCC patients had higher prevalence of CAGE positivity (28% SCC vs 11% IPC, p <0.0001), ESAS SDS(p=0.0134), depression(p=0.0009), anxiety(p=0.0097) and sleep(p=0.0015); MDAS scores were significantly higher in IPC (p<0.0001).115/400 patients (29%) utilized SCCTP. 96/115 outpatients (83%) used the SCCTP vs 19/115 IPC (17%). Common reasons for calls were pain (24%), pain medication refills (24%) and counseling (12%). Of 115 phone calls, 340 recommendations were made; 43% (145/340) were regarding care at home; 56% of these recommendations were regarding opioids. Patients who utilized SCCTP had worse pain(p=0.0059), fatigue(p=0.0448), depression(p=0.0410), FWB(p=0.0149) and better MDAS scores(p=0.0138) compared to non-utilizers. CONCLUSIONS There was more frequent SCCTP use by outpatients than inpatients. Most common reason for utilization was pain control. Frequently, recommendations were made to continue symptom management at home. Patients who utilized SCCTP had worse pain, fatigue, depression, well-being scores and better delirium scores.

The conversion ratio from intravenous (IV) hydromorphone to oral (PO) opioids in patients with cancer.

197 Background: Inpatients with cancer frequently undergo conversions from IV to PO hydromorphone (HM) or opioid rotation (OR) from IV HM to another PO opioid prior to discharge. Currently used conversion ratios (CR) between IV and PO HM range from 2-5 and opioid rotation ratios (ORR) between IV HM and oral morphine equivalent daily dose (MEDD) range from 10-20. This large variation in ratios may lead to uncontrolled pain or overdosing. Our aim was to determine the accurate CR from IV to PO HM and ORR from IV HM to PO morphine and oxycodone (measured as MEDD). METHODS We reviewed records of 4745 consecutive inpatient palliative care consults in our institute during 2010-14 for patients who underwent conversion from IV to PO HM or OR from IV HM to PO morphine or oxycodone. Patient characteristics, symptoms and opioid doses were determined in patients successfully discharged on oral opioids without readmission within 1 week. Linear regression analysis was used to estimate the CR or ORR between the 24 hour IV HM mg dose prior to conversion to PO and the oral opioid mg dose used in the 24 hours prior to discharge. RESULTS Among 394 eligible patients on IV HM, 147 underwent conversion to PO HM and 247 underwent OR to oral morphine (163) or oxycodone (84). Mean age was 54 years, 39% were male, and 95% had advanced cancer. Median time between conversion to PO and discharge was 2 days. In 147 patients the median CR (IQR) from IV to PO HM was 2.5 (2.1-2.7) and correlation of IV to PO dose of HM was .95 (P < .0001). The median CR was 2.5 in patients receiving < 30mg of IV HM/day and 2.1 in patients receiving ≥ 30mg of HM/day (P = .004). In 247 patients the median ORR (IQR) from IV HM to MEDD was 11.5 (10-13) and correlation of IV HM to MEDD was .93 (P < .0001). The median ORR was 11.5 in patients receiving < 30mg of IV HM/day and 9.9 in patients receiving ≥ 30mg of HM/day (P = .0004). ORR from IV HM to MEDDs obtained from morphine (11) and oxycodone (12.1) were significantly different (P = .0023). The CR and ORR were not significantly impacted by other variables. CONCLUSIONS The median CR from IV to PO HM is 2.5 and ORR from IV HM to MEDD is 11.5. This implies that 1 mg IV HM is equivalent to 2.5 mg PO HM and 11.5 mg MEDD. HM may cause hyperalgesia at doses ≥ 30 mg/day and thereby requires a lower ORR to other opioids.

Exploring the preferences for place of death among cancer patients and their caregivers.

40 Background: Understanding the preferred place of death (POD) for advanced cancer patients (Pts) is very important when they are approaching the end of life. Meeting the preferences of Pts is considered an important palliative care (PC) outcome. Prior studies reported that more than 80% of Pts with terminally ill cancer prefer to die at home. In many countries such as the UK, Italy, Greece, South Korea and Japan home deaths have been falling, but in some states of the US and Canada there are indications of a reversal of trends. Dying at home may be more difficult for Pts in severe physical and psychosocial distress, or when there are social or financial difficulties. The purpose of this study was to determine POD preference among PC Pts in the outpatient center (OC) and the palliative care unit (PCU). METHODS A sectional anonymous questionnaire was administered to advanced cancer Pts and caregivers (PCU patients and OC) between August 2012 and September 2014. PCU Pts responded when there was no delirium and the primary caregiver responded when the patient was unable to respond. In the case of outpatients dyads (patient and caregiver) were assessed. RESULTS Overall 141/216 (65%) preferred home death. PCU patients preferred home death less than outpatients. Patient and caregiver agreement regarding preferred place of death was 86% (p <0.001). The preferred POD was the same as one month ago for 82/99 (83%) PCU Pts and 111/116 (96%) outpatients, with significant difference between groups (p=0.002). CONCLUSIONS Although home is the preferred POD in advanced cancer Pts, a substantial minority prefer hospital death or no difference. Patients admitted to the PCU have a higher preference for hospital death in comparison to the outpatients, likely reflecting more severe distress because they already tried home care. Pts and caregivers agree on POD in most cases. Personalized assessment of POD preference for both patient and caregiver is needed. [Table: see text].

Caregiver symptom burden assessment using the Edmonton Symptom Assessment System (ESAS): A preliminary report.

227 Background: Regular assessment of caregiver symptom burden during patient visits would allow prompt referral for their care. The ESAS is a multidimensional tool used in patients but not caregivers. The objectives of this study were to determine the feasibility of the ESAS in assessing caregiver symptoms defined as completing 9/12 items, assess caregiver-reported usefulness of its completion, determine the association of symptom scores between patients, caregivers and various clinical and psychosocial factors, and determine concurrent validity with the Zarit Burden Interview-12 (ZBI-12). METHODS A prospective study of 90 patient-primary caregiver dyads in an outpatient Supportive Care Center in a cancer center was conducted. The 12 item ESAS-FS was completed by the dyads with other measures of clinical and psychosocial factors [demographics, cancer diagnosis, co-morbidities, caregiving activities, prognostic index and patients performance status]. RESULTS The ESAS is a feasible tool to assess caregiver symptom burden with 90/90 caregivers [100%] completing at least 9/12 items; 66/90 caregivers [73%] found ESAS useful to report their symptom burden. A significant association was found between ESAS scores of caregivers and patients in depression [p < 0.01], psychosocial items [depression, anxiety, well-being, financial distress, spiritual pain; p < 0.01], and total symptom distress scores [p < 0.01]. Caregiver employment status [p = 0.03] and total caregiver activities [p = 0.04] were significantly associated with total caregiver ESAS scores. There was no significant association between patient and caregiver co-morbidities [p = 0.08], prognostic index [0.07] and performance status [p = 0.26] to total caregiver ESAS scores. Caregivers recommended certain physical symptoms such as pain and nausea may be eliminated. Concurrent validity with ZBI-12 was not achieved [r = 0.53, p = 0.74] suggesting that ESAS measured different caregiver dimensions. CONCLUSIONS The ESAS is a feasible tool to measure caregiver symptoms and was found useful by caregivers. Further research is needed to modify the ESAS based on caregivers recommendations and further psychometric studies need to be conducted.