Non-invasive methods for PCA in pain management

Patient controlled analgesia (PCA) with an intravenous opioid has become one of the most effective techniques in the management of acute postoperative pain. In order to increase patient convenience non-invasive patient controlled analgesia by different routes of drug administration has been developed. This article gives a short review of transdermal, nasal, and oral PCA which are currently under extensive investigation.     

Opioid titration in cancer pain: A critical review

Initiation of therapy with strong opioids is a challenging phase to obtain the maximum benefit and to gain the patient's compliance. The approach could be different, depending on the clinical situation and type of opioid regimen. Substantially, the need to titrate the dose of strong opioids emerges in different conditions: (a) in opioid-naive patients who require an opioid treatment; (b) in patients no longer responsive to weaker drugs requiring strong opioids; (c) in patients already receiving strong opioids requiring higher doses because of an increase in pain intensity or a new acute pain problem; (d) in patients who are severely suffering and need an intensive as well as rapid intervention, due to previous persistent undertreatment. Whilst there is a vast literature confirming the effectiveness of most opioid drugs for the treatment of chronic pain, there is a lack of information regarding opioid titration. This review assesses the principal titration methods and outcomes regarding the different opioid drugs and their modalities of administration, in different clinical contexts.     

Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery

BackgroundOctreotide acetate is an 8-amino-acids synthetic octapeptide analogue of somatostatin with much-enhanced duration of action and lower incidence of side effects. We assessed the utility of using intravenous octreotide as an adjuvant to opioid analgesia that might exert a post-operative opioid-sparing effect.MethodsForty-four patients were randomly allocated, to receive either a placebo or intraoperative octreotide 0.33 μg kg^?1 h^?1 intravenous infusion that was maintained in the post-operative period. Patients received for post-operative analgesia an intravenous piritramide patient controlled analgesia (PCA), set to deliver a piritramide 0.02 mg kg^?1 dose.ResultsTwo-way ANOVA revealed significantly fewer (P = 0.0003) mean ± SD weighted piritramide dose requirements in the octreotide group (19.5 ± 6.3 μg kg^?1 h^?1) than in the control group (35.7 ± 8.2 μg kg^?1 h^?1). Dunnett’s two-sided multiple-comparison post hoc test revealed a significant difference between the two groups during the first 22 post-operative hours, following which there were no differences between the two groups. There were no significant differences over time in the mean arterial pressure (P = 0.722), heart rate (P = 0.579) and respiratory rate (P = 0.823) between the octreotide group (80 ± 10 mm Hg, 74 ± 12, 14 ± 2) and the control group (82 ± 9 mm Hg, 76 ± 11, 15 ± 3), respectively.ConclusionWe demonstrated that perioperative octreotide intravenous infusion could be an adjuvant to opioid analgesia as it exerted a piritramide opioid-sparing effect. We encountered more systemic side effects such as nausea, abdominal discomfort, and diarrhea in the octreotide group than in the control group. Our findings could be beneficial to patients who cannot tolerate the adverse effects of opioids.     

病人自控镇痛在英国成人病人术后疼痛管理中的应用及启示

介绍了英国布里斯托皇家医院成人术后疼痛管理中病人自控镇痛(PCA)的临床应用、护理,结合我国临床PCA使用现状进行分析讨论。认为我国可以借鉴西方PCA管理中的经验,以促进病人术后无痛,达到优质护理的目标。     

Safety and efficacy of fentanyl administered by patient controlled analgesia in children with cancer pain

Background Pain is the most common discomfort experienced by children with cancer and occurs in almost 89% of patients in an advanced stage of the disease. It is most often not adequately treated because of inexperience and unfounded fears of analgesic treatment. In adults, patient controlled analgesia (PCA) is widely administered, while in children with moderate to severe cancer pain its use is still under evaluation for safety and efficacy. Goals of work To evaluate the efficacy and safety of fentanyl administered by PCA in children with cancer pain. Materials and methods Eighteen children (range 6 to 15 years) with moderate to severe pain were enrolled and treated with fentanyl by PCA plus background infusion (BI) (BI of 1 μg/kg/h with booster doses of 1 μg/kg by intravenous route). To evaluate efficacy and safety of the analgesic treatment, different subjective and objective parameters were monitored at 4-h intervals. In addition, patients’ satisfaction was assessed by a questionnaire at the end of the treatment. Main results All children experienced a good degree of analgesia and did not require any other analgesic drug during the treatment. Both subjective and objective parameters improved after starting pain-relieving treatment and no major side effects occurred. The questionnaire administered to the children showed a high grade of satisfaction. Conclusions PCA plus BI with fentanyl administered by intravenous route is a safe and efficacious method for analgesia in children with moderate to severe cancer pain. Our policy of fentanyl-treatment did not show any major side effects.     

Use of patient-controlled analgesia for pain control in dying children

Background In the last week of life, the daily opioid dose in children is highly variable, making the use of patient-controlled analgesia (PCA) a useful therapy option. Scientific data on the use of PCA in paediatric palliative care are rare. Materials and methods Retrospective chart review over a 7-year period (Jan 1998–Jan 2005) of PCA treated children dying of cancer was used. Results Eight children were on PCA for a median duration of 9 days (range, 1 to 50). The daily median intravenous morphine equivalent dose referenced to body weight increased significantly when PCA was initiated and during the last week of life. In the last week of life, the median daily number of delivered and undelivered bolus requests ranged from 7.5–21 and 0–4.5, respectively. To meet children’s individual needs, 39 PCA parametre changes on 22 opportunities were performed. Median daily mean pain scores remained low (range, 0–3; numerical rating scale 0–10) throughout the period. Conclusion PCA proved an ideal, dependable and feasible mode of analgesic administration for the individual titration of dose to effect.     

Addition of a second opioid may improve opioid response in cancer pain: preliminary data

Recent experimental data suggest a possible use of an opioid combination to improve analgesia. In cancer patients, a rapid opioid escalation due to either worsening of the pain condition or the development of tolerance is a critical phase, as this condition is associated with a negative prognosis. The aim of this study was to assess the effects of adding a second opioid at low doses in patients with a poor analgesic benefit after dose escalation. Fourteen patients receiving strong opioids who had increased their dosage more than 100% in the last week unsuccessfully were randomly chosen to add a second opioid to the first using an initial equivalent dosage of 20% of the previous therapy. The dose of the second opioid was then changed according to the clinical situation to obtain an acceptable pain control with minimal adverse effects. Pain and symptoms associated with opioid therapy were assessed, and an opioid escalation index (OEI) was calculated at weekly intervals. OEI significantly decreased after adding the second opioid, and this trend was also maintained for the following weeks. Similarly, pain intensity was significantly improved and maintained at acceptable levels for the following weeks. The second opioid did not induce significant opioid-related adverse effects. The opioid combination was able to break opioid escalation in patients with pain syndromes with a poor response to the previous opioid. It allowed for a regaining of analgesia, regardless of the opioid combination used. These preliminary observations should be confirmed in further studies.     

Continuous infusion of opioid drugs in the treatment of cancer pain: Guidelines for use

Continuous intravenous infusion of opioid drugs is a commonly applied approach to the management of cancer pain. Though rare studies, clinical surveys and anecdotal reports have generally concluded that the technique is both safe and efficacious, the supporting literature is meager, and neither clinical indications nor guidelines for use have been clearly defined. This report reviews the available literature on the use of continuous opioid infusion and proposes guidelines for management in the cancer population. Controlled, prospective trials of this method of drug administration are needed.     

以护士为核心的新型疼痛管理模式在临床应用研究

目的：探讨以护士为核心的新型疼痛管理模式,为术后患者疼痛的管理提供科学的经验。方法：选择2016年5月至2017年4月在我院行胸、腹微创手术的患者,共212名。随机分为干预组106例,对照组106例。对照组按常规方式进行术后疼痛管理;干预组由护士进行常规疼痛管理外,同时参与患者自控式镇痛(PCA)泵的管理。结果：各研究组中没有明显药物不良反应发生。干预组停泵率明显低于对照组。在胸部手术后行静脉镇痛的患者中干预组的镇痛效果优于对照组;其他治疗组间的镇痛效果比较虽无差异,但干预组的额外用药量却显著降低。研究证明通过以护士为核心,多学科协作的疼痛管理,使自控式镇痛泵得到了充分应用,额外镇痛药物的用药量明显减少。结论：以护士为核心的多学科协作管理模式在术后镇痛管理中具有很大的优势,起到了重要的作用。     

Intravenous opioid testing in patients with chronic non-cancer pain.

The clinical use of an intravenous opioid testing can help to predict whether opioids will be beneficial. The determination of individual opioid responsiveness justifies subsequent long-term opioid treatment and is generally recommended. An overview over current testing procedures is given with particular regard to choice of opioid, maximum dose, determination of endpoints and duration of testing and recovery. Remifentanil testing is a new approch and is studied in a randomized placebo-controlled cross-over study in 24 patients suffering from severe non-cancer pain. An ascending infusion of remifentanil and placebo respectively was titrated against endpoints. The testing allowed a disctinction between 11 opioid-responders and 13 non-responders. Complete recovery after end of infusion was rapid with a reach of baseline conditions after 25 min in all patients. Thus the complete remifentanil testing procedure required at utmost 1 h. In conclusion, remifentanil testing offers a more rapid procedure allowing the routine use in an ambulatory setting.     

A longitudinal study of the efficacy of a comprehensive pain rehabilitation program with opioid withdrawal: comparison of treatment outcomes based on opioid use status at admission

Use of opioids for chronic non-cancer pain is controversial and the efficacy of comprehensive pain rehabilitation programs (CPRPs) that incorporate opioid withdrawal requires further investigation. We test the hypothesis that patients with chronic pain and longstanding opioid use who undergo opioid withdrawal in the course of rehabilitative treatment will experience significant and sustained improvement in pain and functioning similar to patients who were not taking opioids. A longitudinal design study compared 373 consecutive patients admitted to the Mayo Clinic Pain Rehabilitation Center at admission, discharge and six-month posttreatment by opioid status at admission. Measures of pain severity, depression, psychosocial functioning, health status, and pain catastrophizing were used to assess between- and within-group differences. Treatment involved a 3-week interdisciplinary pain rehabilitation program focused on functional restoration. Over one-half of patients (57.1%) were taking opioids daily at admission. The majority of patients (91%) completed rehabilitation and 70% of patients who completed the program returned questionnaires six months posttreatment. On admission, patients taking low- and high-dose opioids reported significantly greater pain severity (P=.001) and depression (P=.001) than the non-opioid group. Significant improvement was found on all outcome variables following treatment (P<.001) and six-month posttreatment (P<.001) regardless of opioid status at admission. There were no differences between the opioid and non-opioid groups upon discharge from the program or at six months following treatment. Conclusion: Patients with longstanding CPRP on chronic opioid therapy, who choose to participate in interdisciplinary rehabilitation that incorporates opioid withdrawal, can experience significant and sustained improvement in pain severity and functioning.     

Transdermal fentanyl and initial dose-finding with patient-controlled analgesia in cancer pain. A pilot study with 20 terminally ill cancer patients

This pilot study evaluated the efficacy and side effects of a combination of initial patient-controlled analgesia (PCA) for dose-finding with transdermal fentanyl administration. Twenty inpatients, requiring strong opioids for severe cancer pain, received intravenous fentanyl on an on-demand basis over a 24-h period. The amount of fentanyl administered was then used as a guideline for selecting a suitable transdermal therapeutic system (TTS) on the 2nd day, which remained in place for 3 days. The size of 2nd TTS, being used from day 5 to 7, was adjusted according to the amount of supplementary intravenous fentanyl doses on day 3. From day 4 to 7 intravenous fentanyl was stopped, and subcutaneous morphine was made available as a rescue medication. A standardized adjuvant medication was allowed. Pain intensity, pain relief, quality of sleep, mood, general state of health, activity, mobility, rescue morphine consumption and side effects were assessed using a diary after baseline pain and symptoms were recorded. Vital functions were monitored and fentanyl plasma levels were measured daily in 15 patients.

The use of TTS fentanyl in combination with initial dose titration using PCA gave rapid and statistically significant pain relief. Patient compliance and acceptance were excellent. In the absence of severe side effects the main complaints were dryness of the mouth and constipation.

Increasing pain intensity and increasing supplementary morphine requirements as well as decreasing plasma fentanyl levels on day 7 may indicate that conversion ratios from intravenous to transdermal administration should be increased or that TTS should be changed earlier. Special indications for this combination may be in patients with dysphagia or vomiting, where pain management could be facilitated.     

多模式镇痛在髋关节置换术后疼痛患者中的应用

目的：探讨多模式镇痛在髋关节置换术后疼痛患者中的应用效果。方法选择全髋关节置换术患者108例,采用随机数字表法随机分为对照组和观察组各54例。对照组患者于术后48 h内给予镇痛泵（ PCA）镇痛,术后48 h停用PCA,改为口服塞来昔布,200 mg／次,bid,口服至术后第6天;观察组患者在给予PCA镇痛基础上,于术后第6小时开始口服塞来昔布,200 mg／次,bid,口服至术后第6天。记录两组患者手术日、术后第1,3,6天髋部切口疼痛,采用数字疼痛分级法（ NRS）评估,比较两组镇痛效果。结果观察组手术日、术后第1,3,6天NRS评分分别为（4．4±1．8）,（4．4±1．5）,（3．5±1．3）,（2．0±1．6）分,均低于对照组,两组比较差异有统计学意义（t值分别为74．131,106．335,223．316,217．195;P＜0．01）。结论采用PCA联合塞来昔布行多模式镇痛可提高髋关节置换术后患者的镇痛效果。     

Gender differences in pain modulation by a sweet stimulus in adults: A randomized study

This study aimed to examine whether or not there are gender differences in sweet stimulus‐induced analgesia for cold pain in adults. In a randomized cross‐over design, twenty men and 20 women held either a 24% sucrose solution or distilled water in their mouth before and while they immersed their hand in cold water and their pain response was examined. Unlike the women, when the men held the sucrose solution in their mouth, the latency of the onset of pain significantly increased, compared with the distilled water. Meanwhile, the level of pain tolerance was not significantly different for both sexes. The findings reveal that the analgesic effect of a sweet stimulus on the pain threshold is influenced by gender differences in human adults, indicating that sweet stimulus‐induced analgesia has a brief analgesic effect, particularly for men. Although more research is warranted, the sweet stimulus could be put to practical application as an adjunct to acute pain management for men.     

Involvement of cytokines, chemokines and adhesion molecules in opioid analgesia.

Tissue destruction is accompanied by an inflammatory reaction. The inflammatory reaction leads to activation of nociceptors and the sensation of pain. Several mediators are responsible for pain and hyperalgesia in inflammation including cytokines, chemokines, nerve growth factor as well as bradykinin, prostaglandins and ATP. Simulatenously however, analgesic mediators are secreted: opioid peptides, somatostatin, endocannabinoids and certain cytokines. Opioid peptides secreted from immune cells are so far the best studied peptides in peripheral inflammatory pain control. This system is hampered for example by anti-adhesion molecule treatment. Novel immunosuppressive drugs for treatment of autoimmune disease targetting cytokines, chemokines or adhesion molecules should therefore be evaluated for potential harmful effects on pain.     

Organic brain syndromes and opioid administration for cancer pain

To clarify the range of potential etiologies that may contribute to organic brain syndrome in patients receiving systemic opioids for cancer pain, we describe 15 patients who presented this complication. In 11 cases, concomitant conditions were found that could contribute to the onset of organic brain syndrome. These data illustrate that multiple causes often play a role in the development of mental status changes in advanced cancer. Opioids are seldom the only causal factor implicated.     

Effectiveness and safety of oral extended-release oxymorphone for the treatment of cancer pain: a pilot study

Goals of work Inadequate analgesia and/or unmanageable adverse events frequently result in the need to rotate patients with cancer pain to a different opioid. The availability of a novel oral extended-release (ER) formulation of oxymorphone provides clinicians with another treatment option. In this study, we assessed the analgesic effectiveness and safety of the new oral ER formulation of oxymorphone following treatment with controlled-release (CR) morphine sulfate or oxycodone.Patients and methods Adults with moderate to severe cancer pain were stabilized for 3 days on morphine CR or oxycodone CR, and then treated for 7 days at their stabilized dose. Drug selection was based upon patients previous use or investigator preference. Patients were then crossed over for 7 days of treatment at an estimated equianalgesic dosage of oxymorphone ER. Pain was assessed using a visual analog scale, and adverse events were recorded.Main results A total of 86 patients entered open-label treatment. Of 34 patients assigned to morphine CR and 52 assigned to oxycodone CR, 21 (61.8%) and 42 (80.8%) completed stabilization and began treatment with oxymorphone ER, respectively; 59 of 63 (93.7%) completed treatment with oxymorphone. There were no significant differences in daily pain intensity scores between oxymorphone ER and comparators (paired t -test). Rescue medication use, expressed as the percent of the daily dose of scheduled opioid, was greater during morphine CR treatment than after crossover to oxymorphone ER (25.2% vs 13.3%; P <0.05, Wilcoxons test). The tolerability/safety profiles (e.g., nausea, drowsiness, somnolence) were similar for all opioids.Conclusions Cancer patients stabilized on morphine CR or oxycodone CR were safely and rapidly converted to a lower milligram dose of oxymorphone ER that provided adequate pain relief with comparable tolerability. These results justify additional trials with oxymorphone ER.This work was supported by Endo Pharmaceuticals Inc., Chadds Ford, PA, and Penwest Pharmaceuticals Co., Danbury, CT.     

Alternatives to opioids for pain management in the emergency department decreases opioid usage and maintains patient satisfaction

Objective

The objective of this study was to assess opioid use in an emergency department following the development and implementation of an alternative to opioids (ALTO)-first approach to pain management. The study also assessed how implementation affected patient satisfaction scores.

Opioid responsiveness in patients with advanced head and neck cancer

The degree of opioid responsiveness in patients with different pain syndromes associated with advanced head and neck cancer was studied with the aid of various indices that have proved to be easy to compare and capable of eliciting individual profiles of opioid responsiveness in cancer patients with pain. Thirty-seven patients requiring opioid therapy for more than 6 weeks were reviewed. The opioid escalation index (OEI) was lower in aged patients, albeit not significantly. Significant differences in OEI were found among patients belonging to the different categories of responses proposed. Although higher doses were needed than reported in the general population, pain was considered acceptable and most patients were classified as partially responsive. Neuropathic pain was associated with higher OEIs. The indices applied will be useful in clinical research to demonstrate individual profiles of opioid responsiveness, from cases of easy and immediate pain control to unresponsiveness to opioid treatment, which can be difficult to evaluate in the clinical setting.