Clinical outcomes of cardiac arrest patients according to opioid use history

PurposeOpioid analgesics are potent respiratory depressants. The purpose of this study was to describe the effects of opioids administered within 24 hours before cardiac arrest on clinical outcomes.Materials and methodsWe retrospectively collected the cardiac arrest data of noncancer patients who were admitted to the general ward of Asan Medical Center from January 2008 to August 2012. We investigated the proportion of these patients who received opioids within 24 hours of a cardiac arrest event, as well as the cardiac arrest characteristics, survival rates, and opioid administration patterns.ResultsOf the 193 patients identified, 58 (30%) had been administered opioids within the previous 24 hours (the opioid group), whereas the remaining 135 (70%) had not been administered opioids (the nonopioid group). The survival rate did not differ significantly between these 2 groups. In the opioid group, as-needed opioid administration was associated with a lower 24-hour survival rate than regular opioid administration (9 [33.3%] of 27 patients vs 20 [64.5%] of 31 patients; P = .030). In multivariate logistic regression analysis, as-needed opioid administration was negatively associated with 24-hour survival.ConclusionsOpioid administration within 24 hours before cardiac arrest per se was not associated with adverse outcomes. However, administration of opioid analgesics on an as-needed basis was associated with poorer survival outcomes than regular dosing. Greater attention should be paid to patients who receive as-needed opioid administration in the general ward.     

Frequency,Indications, Outcomes,and Predictive Factors of Opioid Switching in an Acute Palliative Care Unit

The aim of this study was to prospectively evaluate the frequency, indications, outcomes, and predictive factors associated with opioid switching, using a protocol that had been clinically applied and viewed as effective for many years. A prospective study was carried out on a cohort of consecutive cancer patients who were receiving opioids but had an unacceptable balance between analgesia and adverse effects, despite symptomatic treatment of side effects. The initial conversion ratio between opioids and routes was as follows (mg/day): oral morphine 100 = intravenous morphine 33 = transdermal fentanyl 1 = intravenous fentanyl 1 = oral methadone 20 = intravenous methadone 16 = oral oxycodone 70 = transdermal buprenorphine 1.3. The switch was assisted by opioids used as needed, and doses were changed after the initial conversion according to clinical response in an acute care setting. Intensity of pain and symptoms associated with opioid therapy were recorded. A distress score (DS) was calculated as a sum of symptom intensity. A switch was considered successful when the intensity of pain and/or DS, or the principal symptom necessitating the switch, decreased to at least 33% of the value recorded before switching. One hundred eighteen patients underwent opioid substitutions. The indications for opioid switching were uncontrolled pain and adverse effects (50.8%), adverse effects (28.8%), uncontrolled pain (15.2%), and convenience (4.2%). Overall, 103 substitutions were successful. Ninety-six substitutions were successful after the first switching, and a further substitution was successful in seven patients who did not respond to the first switch. The mean time to achieve dose stabilization after switching was 3.2 days. The presence of both poor pain control and adverse effects was related to unsuccessful switching (P < 0.004). No relationship was identified between unsuccessful switching and the opioid dose, opioid sequence, pain mechanism, or use of adjuvant medications. Opioid switching was an effective method to improve the balance between analgesia and adverse effects in more than 80% of cancer patients with a poor response to an opioid. The presence of both poor pain relief and adverse effects is a negative factor for switching prognosis, whereas renal failure is not.     

Palliative sedation in advanced cancer patients followed at home: a retrospective analysis

ContextData regarding palliative sedation at home in dying patients are lacking.ObjectivesTo describe the frequency, indication, and modality of palliative sedation (PS) in patients followed at home.MethodsA retrospective analysis of home care cancer patients was performed. Patients who received PS before dying were selected and information about epidemiologic characteristics, indications, duration, drugs, and outcomes was collected.ResultsOf 370 medical charts of patients who died at home, 49 patients received PS before dying. PS was proposed by the team, relatives, or both in 63.3%, 4.1%, and 32.6% of cases, respectively. Delirium alone or in combination with other symptoms was the most frequent indication to begin PS. Midazolam was the most frequently used drug to initiate PS (98%), at a mean dose of 28.1 mg/day, in combination with parenteral morphine (84.7%) at a mean dose of 25.4 mg/day. At the time of death, midazolam was administered in 98% of patients (mean dose 22.3 mg/day), combined with parenteral morphine in 87.8% of patients (mean dose 28.1 mg/day). Satisfaction for physicians and principal caregivers after PS was good in 46 and 48 cases, respectively.ConclusionPS at home seems to be a feasible treatment option among selected patients and makes a potentially important contribution to improving care for those who choose to die at home.     

Analgesic efficacy and adverse effects of epidural morphine compared to parenteral opioids after elective caesarean section: A systematic review

BackgroundThe optimal effective dose of epidural morphine that provides postoperative analgesia after caesarean section with minimal side effects remains debated.AimsWe performed a systematic review to assess the analgesic efficacy and the incidence of adverse effects of epidural morphine after caesarean section compared to systemic analgesia with opioids.MethodsWe searched Medline, Embase and Cochrane Collaboration Library databases. Studies were evaluated with the Modified Oxford Scale. Prospective randomized studies comparing analgesic efficacy and/or adverse effects of a single epidural morphine administration versus systemic opioids after elective caesarean section were included.ResultsTen studies (n = 431) were selected. Epidural morphine increases the time until the first request for a rescue analgesic (Emax, 29.7 h; 95% confidence interval, 25.2–33.9) and decreases pain scores and postoperative morphine request during the first 24 h compared to systemic opioid analgesia. However, epidural morphine increases the incidence of pruritus (relative risk, 2.7; 95% CI, 2.1–3.6) and nausea (relative risk, 2.0; 95% CI, 1.2–3.3).ConclusionsA single bolus of epidural morphine provides better analgesia than parenteral opioids but with an effect limited to the first postoperative day after caesarean section and with an increase in morphine side effects.     

Opioid overdose leading to intensive care unit admission: Epidemiology and outcomes

PurposeThere is a scarcity of studies assessing the patient population admitted to the intensive care unit (ICU) with opioid overdose. We sought to characterize the epidemiologic features and outcomes of this patient population.Materials and methodsThis is a retrospective cohort study of adult patients admitted to the ICU at University of Louisville Hospital for opioid overdose. We reviewed each patient's hospital record for demographic data, comorbidities, opioid used, coingestions, and outcomes.ResultsWe included 178 adult patients, of which 107 (60%) were females. The median age was 41 years (interquartile range [IQR], 23). Oxycodone and hydrocodone were the 2 most commonly abused opioids. Benzodiazepines were the most common drug coingested, followed by amphetamines. Tobacco smoking, chronic pain, and alcoholism were the most frequent comorbidities identified. Mental disorders were also common. Most patients required invasive mechanical ventilation (84.8%). Median ICU length of stay was 3 days. Eighteen patients (10.1%) died in the hospital, whereas 6 patients (3.4%) were discharged to a nursing home. Patients who had any coingestion were significantly more likely to undergo invasive mechanical ventilation (91% vs 77%; P = .014) and had longer ICU length of stay (3 [IQR, 2] vs 2 [IQR, 1.8] days; P = .024).ConclusionOpioid overdose is a common cause of ICU admission and affects a relatively young population. Most have respiratory failure requiring mechanical ventilation. It is associated with a relatively high inhospital mortality. Coingestions appear to have an impact on outcomes.     

Patterns of opioid use for chronic noncancer pain in the Veterans Health Administration from 2009 to 2011

Although opioids are frequently prescribed for chronic noncancer pain (CNCP) among Veterans Health Administration (VHA) patients, little has been reported on national opioid prescribing patterns in the VHA. Our objective was to better characterize the dosing and duration of opioid therapy for CNCP in the VHA. We analyzed national VHA administrative and pharmacy data for fiscal years 2009 to 2011. For individuals with CNCP diagnoses and any opioid use in the fiscal year, we calculated the distribution of individual mean daily opioid dose, individual total days covered with opioids in a year, and individual total opioid dose in a year. We also investigated the factors associated with being in the top 5% of individuals for total opioid dose in a year, which we term receipt of high-volume opioids. About half of the patients with CNCP received opioids in a given fiscal year. The median daily dose was 21 mg morphine equivalents. Approximately 4.5% had a mean daily dose higher than 120 mg morphine equivalents. The median days covered in a year was 115 to 120 days in these years for those receiving opioids. Fifty-seven percent had at least 90 days covered with opioids per year. Major depression and posttraumatic stress disorder were positively associated with receiving high-volume opioids, but nonopioid substance use disorders were not. Among VHA patients with CNCP, chronic opioid therapy occurs frequently, but for most patients, the average daily dose is modest. Doses and duration of therapy were unchanged from 2009 to 2011.     

Rate of patients at elevated risk of opioid overdose visiting the emergency department

Objective

To determine the rate of patients visiting the emergency department who are at risk of opioid overdose.

"I feel uncomfortable 'calling a patient out'": educational needs of palliative medicine fellows in managing opioid misuse

ContextDuring the past 10 years, advocates of palliative care have sought to be included earlier in the course of patients’ illnesses. Palliative care providers may thus be more likely to care for patients who misuse and abuse opioids.ObjectivesTo assess whether hospice and palliative medicine (HPM) fellows see patients at risk for opioid misuse and how competent they perceive themselves to be to treat pain in these patients.MethodsAn electronic survey was distributed to 102 HPM fellows. The survey included questions assessing self-perceived competency in care for patients who misuse opioids. Responses were rated using a Likert scale of one to seven, where one = strongly agree and seven = strongly disagree; any number greater than two was considered to be nonagreement.ResultsFifty-seven (56%) fellows from 34 programs responded to the survey. In the previous two weeks, 77.2% of respondents had seen at least one patient with a substance use disorder (SUD) and 43.9% had treated a patient whom they were concerned was misusing opioids. Half (47.2%) of respondents stated that they have a working knowledge of addiction, 41.4% agreed their training has prepared them to manage opioid misuse, and 36.8% felt they knew how to differentiate pain from addiction. Only 21.1% were satisfied with how they treat symptoms in this population. Fellowship training in opioid misuse was associated with increased satisfaction.ConclusionHPM fellows regularly see patients who are at risk for opioid misuse and feel unprepared to treat pain in these patients. There is a need for more education of fellows in this area.     

The Role of a Low-Dose Ketamine-Midazolam Regimen in the Management of Severe Painful Crisis in Patients With Sickle Cell Disease

ContextAcute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration.ObjectivesWe studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis.MethodsA retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25 mg/kg, followed by infusion of 0.2–0.25 mg/kg/h. A midazolam bolus of 1 mg followed by infusion of 0.5–1 mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis.ResultsNine patients were assessed, with mean age of 27 ± 11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean ± SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6 ± 16.5, and it was 112 ± 12.2 on Day 1 (D1) of ketamine treatment (P = 0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P = 0.01).ConclusionLow-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect.     

A Randomized,Double-Blind,Placebo-Controlled Study of Fentanyl Buccal Tablets for Breakthrough Pain: Efficacy and Safety in Japanese Cancer Patients

ContextRapid-onset opioids for treating breakthrough pain (BTP) in patients with cancer are needed in the Japanese care setting.ObjectivesTo examine the efficacy and safety of fentanyl buccal tablets (FBTs) for treating BTP in Japanese cancer patients.MethodsThis was a randomized, double-blinded, placebo-controlled study. In subjects receiving around-the-clock (ATC) opioids at doses of 30 mg or more to less than 60 mg or 60–1000 mg of oral morphine equivalents (low and high ATC groups), dose titration was started from 50 to 100 μg FBT, respectively. Subjects whose effective dose was identified were randomly allocated to a prearranged administration order of nine tablets (six FBTs and three placebos), one tablet each for nine episodes of BTP (double blinded). Efficacy and safety of FBT were assessed for patients overall, and also for the low and high ATC groups.ResultsA significant difference was observed between FBT and placebo for the primary endpoint of pain intensity difference at 30 minutes. The analgesic onset of FBT was observed from 15 minutes in several secondary variables (e.g., pain relief). Adverse events were somnolence and other events associated with opioids were mostly mild or moderate. Of the low and high ATC group subjects, an effective FBT dose was identified in 72.2% and 73.1%, respectively.ConclusionThe safety of FBT and its analgesic effect on BTP were confirmed in Japanese cancer patients receiving opioids. Our findings suggest that analgesic onset may occur from 15 minutes after FBT, and that FBT can be administered to patients with low doses of ATC opioids.     

Efficacy and safety of morphine-6-glucuronide (M6G) for postoperative pain relief: A randomized,double-blind study

AimsThe aim of the study was to assess analgesia and safety effects of a range of intravenous doses of M6G (10, 20 and 30 mg/70 kg), compared to placebo, in postoperative patients.MethodsIn a randomized, multicentre, double-blind study, patients undergoing knee replacement surgery under spinal anaesthesia were administered one of three doses of M6G, or placebo, 150 min after spinal nerve block. Morphine rescue medication was available via a PCA pump. The key index of analgesic activity was determined as the amount of morphine consumed by the patient over 12 and 24 h after M6G administration. Time to first use of rescue medication, VAS and global pain assessment scales were also recorded. Safety was assessed by monitoring supine blood pressure, heart rate, respiratory rate and body temperature and typical opioid side-effects of PONV and sedation.ResultsA total of 170 patients were dosed with study medication. M6G induced a dose-related reduction in morphine use over 24-h that reached statistical significance compared to placebo at M6G 30 mg/70 kg. There was no clear relationship between M6G dose and time to first use of PCA morphine. Pain relief was similar in all groups. M6G showed small, but inconsistent effects on the cardiovascular system and on sedation and no effects were observed on respiration or PONV.ConclusionM6G induced long-lasting dose-related analgesic effects in postoperative patients with limited effects on cardiorespiratory systems or of opioid-like side-effects. M6G is an effective opioid for the treatment of moderate to severe postoperative pain.     

Management of Moderate-to-Severe Dyspnea in Hospitalized Patients Receiving Palliative Care

ContextBenzodiazepines (BZDs) are commonly prescribed for relief of dyspnea in palliative care, yet few data describe their efficacy.ObjectivesTo describe the management of moderate-to-severe dyspnea in palliative care patients.MethodsChart review of inpatients with moderate or severe dyspnea on initial evaluation by a palliative care service. We recorded dyspnea scores at follow-up (24 hours later) and use of BZDs and opioids.ResultsThe records of 115 patients were reviewed. The mean age of patients was 64 years and primary diagnoses included cancer (64%, n = 73), heart failure (8%, n = 9), and chronic obstructive pulmonary disease (5%, n = 6). At initial assessment, 73% (n = 84) of the patients had moderate and 27% (n = 31) had severe dyspnea. At follow-up, 74% (n = 85) of patients reported an improvement in their dyspnea, of which 42% (n = 36) had received opioids alone, 37% (n = 31) had BZDs concurrent with opioids, 2% (n = 2) had BZDs alone, and 19% (n = 16) had received neither opioids nor BZDs. Logistic regression analysis identified that patients who received BZDs and opioids had increased odds of improved dyspnea (odds ratio 5.5, 95% CI 1.4, 21.3) compared with those receiving no medications.ConclusionMost patients reported improvement in dyspnea at 24 hours after palliative care service consultation. Consistent with existing evidence, most patients with dyspnea received opioids but only the combination of opioids and BZDs was independently associated with improvement in dyspnea. Further research on the role of BZDs alone and in combination with opioids may lead to better treatments for this distressing symptom.     

Lack of Benefit From Paracetamol (Acetaminophen) for Palliative Cancer Patients Requiring High-Dose Strong Opioids: A Randomized,Double-Blind,Placebo-Controlled,Crossover Trial

ContextThe adjunctive use of paracetamol (acetaminophen) with strong opioids has become entrenched practice in palliative care pain management, despite little evidence to support its use.ObjectiveThe study aim was to investigate potential analgesic benefits of 4 g of paracetamol daily for palliative cancer patients requiring high-dose opioids.MethodsThirty-one patients, using at least 200 mg of oral morphine equivalent daily, were recruited to a prospective, double-blinded, randomized, crossover trial. Patients received usual medications plus 4 g of paracetamol or placebo for five days each in random order. Primary outcome, effect on pain, was assessed using daily diaries, including a numerical rating scale (NRS) from zero (no pain) to 10 (unbearable) and recording numbers of breakthrough analgesics. Secondary outcomes—nausea, vomiting, cognitive impairment, constipation, and overall well-being—were assessed using the NRS. Data from the last four days of each treatment were analyzed. Patients also indicated in which part of the study their pain was better controlled.ResultsTwenty-two patients, requiring a median dose of 255 mg of oral morphine equivalent daily, completed the trial. There were no significant order or treatment-by-order interaction effects for any variable; paired t-tests were conducted to investigate change in mean levels on outcome variables with placebo vs. paracetamol. For none of the variables was there a statistically significant difference when assessed with placebo compared with paracetamol. No change approached clinically significant levels, with a mean difference in rated pain of 0.16, and mean difference of 0.42 for a number of breakthrough medications. Fifteen patients were undecided whether paracetamol improved pain.ConclusionsThese data do not support the common practice of adding regular paracetamol daily as an adjunct to high-dose opioids for pain control in cancer patients receiving palliative care.     

Association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with advanced cancer

ContextPatients with advanced cancer often experience symptoms such as pain, anorexia, and fatigue. Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patient’s symptom burden.ObjectivesTo examine the association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with cancer.MethodsA retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia. We collected information regarding cortisol levels (am or random), testosterone levels (men only), morphine equivalent daily dose (MEDD), and symptom severity measured by the Edmonton Symptom Assessment Scale. Nonparametric correlation analysis was performed.ResultsThe median age was 63 years (range 24–79), and 62% were men (n = 48). Most patients had gastrointestinal (n = 33, 43%) or thoracic (n = 21, 27%) malignancies and were Caucasian (n = 46, 60%). The median random cortisol level was 19.1 μg/dL (Q1–Q3, 13.4–23.8 [normal, 4.3–22.4]), which correlated with MEDD (Spearman coefficient, 0.25, P = 0.032) and symptoms including pain (0.50, P < 0.001), fatigue (0.29, P = 0.012), nausea (0.34, P = 0.003), depression (0.24, P = 0.032), and anxiety (0.25, P = 0.031). Pain and nausea remained significant after Bonferroni correction. Median morning cortisol level (n = 28) was 20.6 μg/dL (Q1–Q3, 16.6–25.4) and significantly correlated with pain (0.55, P = 0.003) after Bonferroni correction. Patients with a MEDD <30 mg/day had a mean random cortisol level of 16.6 μg/dL, whereas patients with a MEDD ≥30 mg/day had a mean random cortisol level of 20.6 μg/dL (P = 0.01). In 44 male patients with cancer, MEDD was inversely correlated with the total testosterone level (?0.52, P = 0.001).ConclusionIn patients with advanced cancer, elevated random cortisol levels were associated with pain and opioid use, although abnormally low levels of cortisol were found to be infrequent. Patients on higher opioid therapy (MEDD >30) had increased cortisol levels, and male patients had lower testosterone levels. Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis. Future studies are needed.     

Palliative Sedation in Patients With Advanced Cancer Followed at Home: A Prospective Study

ContextHome care programs in Italy.ObjectivesThe aim of this study was to assess a protocol for palliative sedation (PS) performed at home.MethodsA total of 219 patients were prospectively assessed to evaluate a PS protocol in patients with advanced cancer followed at home by two home care programs with different territorial facilities. The protocol was based on stepwise administration of midazolam.ResultsA total of 176 of the patients died at home, and PS was performed in 24 of these patients (13.6%). Younger patients received the procedure more frequently than older patients (P = 0.012). The principal reasons to start PS were agitated delirium (n = 20) and dyspnea (n = 4). Mean duration of PS was 42.2 ± 30.4 hours, and the mean doses of midazolam were 23–58 mg/day. Both the home care team and the patients' relatives expressed optimal or good levels of satisfaction with the procedure in all but one case, respectively.ConclusionThis protocol for PS was feasible and effective in minimizing distress for a subgroup of patients who died at home. The characteristics of patients who may be effectively sedated at home should be better explored in future studies.     

Effectiveness and Tolerability of Amidotrizoate for the Treatment of Constipation Resistant to Laxatives in Advanced Cancer Patients

ContextConstipation is a common problem for advanced cancer patients, and is generally inadequately treated.ObjectivesThe aim of this study was to prospectively evaluate the effectiveness and tolerability of amidotrizoate (AM) in patients unresponsive to current laxatives.MethodsA consecutive sample of advanced cancer patients was surveyed. Inclusion criteria were no bowel movements for three days despite receiving regular doses of senna or lactulose. AM 50 mL was administered orally; the dose could be repeated the day after, based on clinical judgment and/or patients’ preference. Age, sex, primary tumor, previous abdominal surgery, chemotherapy and radiotherapy performed in the previous month, and the use of opioids were recorded. Nausea, the presence of early satiety, and fluid and food intake also were measured. Time to first bowel movement was recorded, and adverse effects attributable to AM.ResultsNinety-nine patients were surveyed (36 women/63 men). The mean age was 65.7 years (SD ± 12.2) and the mean Karnofsky score was 46.8 (SD ± 9.4). Patients had no bowel movement for a mean of four days (SD ± 1.8, range 3–15 days). A total of 80.8% of patients were receiving opioids in doses of mean daily oral morphine equivalents of 164 mg (SD ± 235). After AM administration (mean 9.9 ± 6.5 hours), 44.4% of patients had a bowel movement within 24 hours. This effect was associated with significant improvement of other symptoms and was independent of age (P = 0.513), gender (P = 0.090), Karnofsky status (P = 0.979), days of constipation (P = 0.198), concomitant chemotherapy (P = 0.098) or radiotherapy (P = 0.414), the use of opioids (P = 0.361), opioid doses (P = 0.420), and primary tumor (P = 0.231). The treatment was more effective in patients who had previous abdominal surgery (HR = 3.33).ConclusionAM was found to be an easy and inexpensive breakthrough medication to induce a bowel movement in about 45% of advanced cancer patients not responsive to common laxatives, with limited and acceptable adverse effects.     

A strategy for conversion from subcutaneous to oral ketamine in cancer pain patients: effect of a 1:1 ratio

ContextNo consensus exists about the most appropriate dose ratio for conversion from parenteral to oral ketamine.ObjectivesTo confirm that a 1:1 dose ratio is suitable for converting subcutaneous (s.c.) to oral ketamine in cancer patients.MethodsPatients with opioid poorly responsive cancer pain, who responded to 0.4, 0.6, or 0.8 mg s.c. ketamine bolus, were treated with 0.1, 0.15, or 0.2 mg/kg/h ketamine infusion, respectively. Switching to the oral route, by applying a 1:1 dose ratio, was carried out in patients who experienced adequate pain relief and continued to need ketamine as a coanalgesic. Pain, somnolence, feelings of insobriety, confusion, and cardiovascular parameters were assessed throughout the process.ResultsTwenty-nine patients were enrolled in the study. Ketamine infusion decreased pain intensity from severe to no pain or slight pain in 23 of 29 and six of 29 patients, respectively. The median of s.c. ketamine doses was 0.2 mg/kg/h (range 0.1–0.5). After oral switching, 27 of 29 patients remained as successfully controlled as when receiving s.c. ketamine. The other two patients needed a slight dose ratio readjustment, to 1:1.3 and 1:1.5, to maintain pain control. The median of oral ketamine doses was 300 mg/day (interquartile range 240–382.5). Seven of 29 patients receiving s.c. ketamine developed moderate and transitory side effects, such as feelings of insobriety and somnolence. No side effects were present while receiving oral ketamine. No significant changes were observed in cardiovascular parameters.ConclusionA 1:1 dose ratio for conversion from s.c. to oral ketamine is safe and effective in cancer pain patients.     

Opioid switch in palliative care, opioid choice by clinical need and opioid availability.

Availability of different WHO-step 3 opioids has encouraged the discussion on their value and led to the concepts of opioid rotation. Rotation is suggested, when other measures fail to achieve optimal analgesia and tolerability in cancer pain treatment. Opioid use was assessed in a prospective cohort study of 412 palliative care patients from 14 inpatient and outpatient palliative care facilities in Germany. The most frequently used opioids at baseline were morphine and fentanyl. The most frequent changes in medication (N=106) occurred from oral to parenteral morphine. Only in 49 cases true switches to other long acting opioids were recorded. This is far less than expected from other reports. True switches and adverse side effects were found to occur more frequently in inpatients, while efficacy problems were more frequently recorded in outpatients. There was no correlation between the opioid used at baseline and switch frequency, but numbers of cases receiving other opioids than fentanyl or morphine were low. Reasons for and frequencies of changes in medication were found to be largely shaped by the setting reflecting patients' needs and clinical necessities. Recommendation of first line therapy and availability of opioid formulations define the frequency of opioid use. This impedes evaluation of specific differences between the opioids.