Non-narcotic Agent Research Articles

Transversus Abdominis Plane Block as Part of a Multimodal Analgesic Regimen in Patients Undergoing Anterior Lumbar Interbody Fusion: A Retrospective Cohort Study.

Opioids are a mainstay for pain control in patients undergoing lumbar spine surgery but are associated with a high risk of dependence and significant adverse effects. Efforts continue to be made to utilize non-narcotic agents such as regional nerve block for pain control as part of a multimodal analgesia regimen. Recently, transversus abdominis plane (TAP) blocks have proven beneficial for patients undergoing lumbar fusion procedures. The purpose of this study is to evaluate the efficacy of TAP blocks for postoperative pain control and the effect on opioid consumption and hospital length of stay (LOS) in patients undergoing anterior lumbar interbody fusion (ALIF). A retrospective review of patients undergoing elective ALIF included collection of data on demographics, LOS, pain scores using visual analog scale (VAS), opioid consumption using morphine milligram equivalents (MME) from postoperative day (POD) 0 to 5, and any complications. Patients who underwent primary ALIF or ALIF with concomitant posterolateral lumbar fusion were included. A total of 99 patients met inclusion criteria; 47 had a preoperative TAP block and 52 did not. Demographic data and number of levels fused were equally distributed between the groups. The TAP group had significantly lower MME consumption postoperatively during POD 0 to 2 and 0 to 5. VAS pain scores were lower for TAP block patients on POD 3 and 4; otherwise, there was no significant difference. LOS and complication rates were not significantly different. A multiple regression analysis found male sex to be a predictor of increased postoperative MME, while age and TAP block were significant predictors of decreased MME. The use of TAP block for patients undergoing ALIF was associated with less cumulative MME consumption in the immediate postoperative period. TAP block may be an effective tool for reducing postoperative opioid consumption in patients undergoing ALIF. The data in this study provide clinical relevance supporting the use of TAP blocks for patients undergoing ALIF procedures.

Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the A3 Receptor Subtype.

Agonists of the Gi protein-coupled A3 adenosine receptor (A3AR) have shown important pain-relieving properties in preclinical settings of several pain models. Active as a monotherapy against chronic pain, A3AR agonists can also be used in combination with classic opioid analgesics. Their safe pharmacological profile, as shown by clinical trials for other pathologies, i.e., rheumatoid arthritis, psoriasis and fatty liver diseases, confers a realistic translational potential, thus encouraging research studies on the molecular mechanisms underpinning their antinociceptive actions. A number of pathways, involving central and peripheral mechanisms, have been proposed. Recent evidence showed that the prototypical A3AR agonist Cl-IB-MECA and the new, highly selective, A3AR agonist MRS5980 inhibit neuronal (N-type) voltage-dependent Ca2+ currents in dorsal root ganglia, a known pain-related mechanism. Other proposed pathways involve reduced cytokine production, immune cell-mediated responses, as well as reduced microglia and astrocyte activation in the spinal cord. The aim of this review is to summarize up-to-date information on A3AR in the context of pain, including cellular and molecular mechanisms underlying this effect. Based on their safety profile shown in clinical trials for other pathologies, A3AR agonists are proposed as novel, promising non-narcotic agents for pain control.

The Comparison of Analgesics and Kinesiological Taping in Rib Fractures

Pain is the most common symptom of rib fractures. In pain control, narcotic and non-narcotic agents, intercostal blockage, epidural catheter, and even rarely surgical intervention and reduction can be applied. The kinesiology taping method has an analgesic effect by reducing edema and inflammation, activating sensory stimuli, descending inhibitory mechanisms, and regulating superficial and deep fascia functions. It has a wide range of indications in pain control including musculoskeletal system mostly. However, no studies have been reported on the application of kinesiology tape in rib fractures. In our study, we aimed to share the results of cases who received oral/parenteral analgesic treatment and those who underwent kinesiology taping. A series of 46 cases with rib fractures due to thoracic trauma were analyzed. The verbal pain scores of group 1 (G1) who had a single rib fracture and to whom kinesiology taping was performed and group 2 (G2) who received analgesic treatment were evaluated. The pain scores of the cases in both groups at the 30th minute; 1st, 3rd, 6th, 12th, and 24th hours; and 3rd day were analyzed. Results were evaluated by Mann-Whitney U tests. p<0.05 was considered significant. There were a total of 23 cases in each group. The mean age of G1 was 53.26 SD17.55 years. The mean age of G2 was 55.86 SD16.37. The mean pain score in G1 after the tape application was 4.78 SD0.79 at the 30th minute, 4.43 SD0.58 at the first hour, 4.08 SD0.59 at the 3rd hour, 3.91 SD0.66 at the 6th hour, 3.86 SD0.75 at the 12th hour, 3.69 SD0.82 at the 24th hour, and 3.82 SD0.57 on day 3. After analgesic treatment, the mean pain score of G2 was found as 7.47 SD0.51 at the 30th minute, 6.86 SD0.34 at the first hour, 6.56 SD0.72 at the 3rd hour, 6.52 SD0.51 at the 6th hour, 5.95 SD0.36 at the 12th hour, 6 at the 24th hour, and 5.21 SD0.51 on day 3. When the pain scores of G1 and G2 were compared, it was found that kinesiology tape was significantly significant (p<0.00001, p<0.05). In conclusion, in reducing pain complaints affecting the quality of life in cases with rib fractures due to thoracic trauma, the application of kinesiology tape significantly reduced the need for analgesics and even eliminated the need in the long term. Following this study, we think that in patients with more fractures or bilateral rib fractures, larger randomized studies should be performed and routine treatment should be included.

Postoperative Pain Management Following Craniosynostosis Repair: Current Practices and Future Directions.

Postoperative analgesia following craniosynostosis repair is a clinical challenge for plastic and reconstructive surgeons. There is a paucity of published data on the postoperative pain associated with craniosynostosis repair procedures and the prescribed analgesia varies with different unit protocols. The authors sought to summarize the current knowledge of the postoperative analgesia following craniosynostosis repair by reviewing the literature for existing regimens, clinical outcomes, and recommendations. Two independent investigators conducted a literature search of the Pubmed, Cochrane, and Google Scholar databases for relevant clinical studies. Studies were abstracted for procedure type, postoperative pain management protocol, pain scores, side effects, complications, and clinical recommendations. Ten studies describing the use of analgesic agents in open craniosynostosis surgery from 2000 to 2018 were fully reviewed, comprising a total of 431 patients undergoing surgical procedures using a combination regimen of narcotic and nonnarcotic agents (n = 315) and nonnarcotic agents alone (n = 116). Multimodal analgesia is the primary regimen used following open craniosynostosis repair procedures. Opioids are a critical component in pain management regimens, relieving patient discomfort. However, due to the deleterious effects that come with their prolonged use, intravenous acetaminophen is currently used as an alternative in many centers. The preferred mode of pain medication administration in the pediatric population is increasingly via the intravenous route which ensures that a full dose of pain medication is given. The authors suggest the use of dexmedetomidine, both an adjunct to intravenous acetaminophen and as a substitute for morphine due to its superior safety and efficacy profile.

Multimodal Analgesia in Outpatient Head and Neck Surgery

Importance Perioperative analgesia strategies that rely solely on narcotics may contribute to adverse effects and concerns about opioid abuse or dependence. Multimodal analgesia protocols incorporating nonnarcotic agents may reduce the need for postoperative narcotic use. Objective To evaluate the feasibility and safety of a multimodal analgesia protocol for outpatient head and neck surgical procedures and to identify the association of the multimodal analgesia protocol with postoperative pain perception scores and patient satisfaction. Design, Setting, and Participants Retrospective evaluation of prospectively collected data on adults who underwent outpatient thyroid, parathyroid, and parotid surgery between July 2016 and February 2017 at the head and neck surgery service of a tertiary care hospital using a multimodal analgesia strategy with use of immediate preoperative acetaminophen and gabapentin, and intention to treat with a nonnarcotic postoperative outpatient analgesia strategy. Main Outcomes and Measures Overall patient satisfaction scores, Overall Benefit of Analgesia Score (OBAS), and median resting and peak pain scores were recorded. Incidence of reliance on a narcotic-based postoperative outpatient analgesia strategy and adverse events related to altered analgesia strategy were identified. Results Sixty-four patients (48 [75%] female; mean [SD] age, 54.6 [14.3] years) underwent outpatient thyroid, parathyroid, or parotid surgery with use of a multimodal analgesia protocol. On a 10-point rating scale, patients reported low resting pain perception scores (median, 2 [range, 0-8]) and peak pain scores (median, 4 [range, 0-9]). The OBAS assessment for composite effectiveness of analgesia indicated a favorable median score of 1 (range, 0-10; permissible range, 0-28, with lower scores better). Thirty-nine (61%) patients were able to avoid postoperative narcotic use on discharge. Fifty-six (88%) patients reported “high” or “very high” satisfaction with the multimodal analgesia strategy. No complications related to bleeding, hematoma, significant adverse events, or readmissions were observed. Conclusion and Relevance A multimodal analgesia strategy was feasible and safe in patients undergoing outpatient head and neck surgery and may reduce the need for narcotic use. It was associated with low pain perception scores, favorable OBAS, and overall satisfaction scores. The role of multimodal analgesia needs additional evaluation through comparative effectiveness assessment vs conventional pain management strategies.

The Relationship Between Pain and Comorbid Health Conditions in People with Chronic Obstructive Pulmonary Disease

Purpose: To determine if pain and pain interference are associated with comorbid health conditions in people living with chronic obstructive pulmonary disease (COPD) and secondly, to determine if specific types of comorbidities are associated with more pain and a particular location of pain. Methods: Ninety-two persons with moderate-tosevere COPD were mailed a package that included: the McGill Pain Questionnaire (MPQ), the Brief Pain Inventory (BPI), and a form to list comorbid health conditions and medications. Results: Of 54 respondents [mean FEV1 48.3%predicted; mean age 72 years], 44 reported pain. On the BPI, 81% of the cohort self-reported pain, of whom 66% had moderate to very severe pain and 73% had moderate to very high pain interference with daily activities. In those who experienced pain, 73% reported >2 comorbid health conditions and 46% reported >3 comorbid health conditions. Cardiovascular (29%) and musculoskeletal health conditions (20%) were the most commonly reported types of comorbid health conditions reported. Those with musculoskeletal or endocrine health conditions reported higher levels of pain. Pain treatments, primarily nonnarcotic agents, were used by 64% of patients. Conclusions: Significant pain and multiple comorbid health conditions are common in people living with COPD and likely compromise full participation in physical activity in some of these individuals.

Predicting Completion of Outpatient Opioid Detoxification with Clonidine

Completion rates for outpatient opioid detoxification with clonidine generally range from 20-40%, but few studies have examined the correlates of successful completion. Of 29 consecutive patients, we compared those who completed detoxification with clonidine (n=12) to those who did not (n=17). Patients who completed treatment were significantly (p< 0.05) more likely to depend on opioids other than heroin, have private health insurance, and report low levels of subjective withdrawal symptoms. Patients with two or three of these characteristics were about seven times more likely to complete treatment than patients with none or one. Although it may not detoxify most opioid-dependent patients, clonidine will likely play a continued role in selected patients when a non-narcotic agent is desirable. The study findings may help target patients who could benefit the most from outpatient clonidine detoxification.

Risk of upper gastrointestinal bleeding associated with non-aspirin cardiovascular drugs, analgesics and nonsteroidal anti-inflammatory drugs.

To evaluate the risk of upper gastrointestinal bleeding associated with non-aspirin cardiovascular drug therapy, common analgesics and individual nonsteroidal anti-inflammatory drugs (NSAIDs). The case group was made up of 1122 consecutive patients admitted with bleeding from a peptic lesion. The 2231 control subjects consisted of 1109 patients hospitalized for other reasons and 1122 outpatients from the same geographical area. The relative risk was calculated by unconditional logistic regression after adjusting for confounding factors. The use of the antiplatelet agent triflusal, and other commonly used cardiovascular drugs, such as beta-receptor blockers and calcium channel blockers, was not associated with increased risk of upper gastrointestinal bleeding. The use of angiotensin-converting enzyme inhibitors reduced the risk of bleeding by 30% (odds ratio 0.7; 95% confidence interval 0.5-0.96). Use of ketorolac (odds ratio 59.4; 95% confidence interval 7.7-454) and piroxicam (odds ratio 19.6; 95% confidence interval 9.3-35.3) carried the highest risk. Use of paracetamol and tramadol was not associated with increased risk of bleeding, but the non-narcotic agent metamizol was associated with a small increase in risk of upper gastrointestinal bleeding (odds ratio 2.6; 95% confidence interval 1.3-5.2). The use of the antiplatelet agent triflusal and other cardiovascular drugs apart from low-dose aspirin was not associated with gastrointestinal bleeding. The use of either NSAIDs or aspirin increased the risk of gastrointestinal bleeding but, among the analgesics, only metamizol induced a small increase in the risk of gastrointestinal bleeding.

Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol.

This report reviews the causes of ocular pain and discusses the pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage of tramadol, a novel non-narcotic oral analgesic. Tramadol is a synthetic analog of codeine with a dual mechanism of action that involves agonist activity at the mu opioid receptor, as well as inhibition of monoaminergic (norepinephrine and serotonin) re-uptake. Unlike opiate analgesics, tramadol has very low propensity toward physical dependence. Common dose-related adverse effects of tramadol include dizziness, nausea, vomiting, dry mouth, and/or drowsiness. Clinically, tramadol has been shown to be equivalent to acetaminophen (325 mg)-codeine (30 mg) combinations for the treatment of moderate or severe nonocular pain. Tramadol appears to be an effective analgesic agent for pain control due to postoperative surgical trauma, as well as in various chronic malignant and nonmalignant disease states. Tramadol has shown variable effectiveness in the control of pain related to dental procedures. The usefulness of tramadol in pain states from ophthalmic origin has yet to be clinically established.

A comparative trial of three agents in the treatment of acute migraine headache

A study was conducted to evaluate the relative efficacy of three non-narcotic agents, chloropromazine, lidocaine, and dihydroergotamine, in the treatment of migraine headache in an emergency department setting. The trial was randomized and single blinded. The study was conducted in two university-affiliated EDs. All patients had an isolated diagnosis of common or classic migraine. Patients were pretreated with 500 mL (IV) normal saline before randomization. Study drugs as administered were dihydroergotamine 1 mg IV repeated after 30 minutes if the initial response was inadequate; lidocaine 50 mg IV at 20-minute intervals to a maximum total dose of 150 mg as required; or chloropromazine 12.5 mg IV repeated at 20-minute intervals to a total maximum dose of 37.5 mg as required. Patients were asked to grade headache severity on a ten-point scale before and one hour after the initiation of therapy. Follow-up by phone was sought the following day. Of 76 patients completing the trial, 24 were randomized to receive chloropromazine, 26 to receive dihydroergotamine, and 26 to receive lidocaine. Reduction in mean headache intensity was significantly better among those treated with chloropromazine (P less than .005). Persistent headache relief was experienced by 16 of the chloropromazine-treated patients (88.9%) contacted at 12 to 24 hours follow-up compared with ten of the dihydroergotamine-treated patients (52.6%) and five of the lidocaine-treated group (29.4%). The relative effectiveness of these three antimigraine therapies appears to favor chloropromazine in measures of headache relief, incidence of headache rebound, and patient satisfaction with therapy.

Relative Addiction Potential of Major Centrally-Active Drugs and Drug Classes- Inhalants and Anesthetics

The inhalation of a wide variety of substances for recreational purposes is a health problem of worldwide proportions. The inhalation of non-narcotic agents, such as volatile inhalants (e.g., solvents and glues), anesthetics and nitrites, adds significantly to the growing number of substance abusers. This is of particular concern because it affects the younger members of the population, and the substances abused are, for the most part, legally obtainable. The toxicity of these inhaled substances are reviewed and compared, as are their potentials for addiction and dependence.

Metamizole: reassessment of its therapeutic role

The use of metamizole is controversial, as reflected in the very different national regulations affecting it. The striking disparities between policies for metamizole made us try to determine if there were reasons to ban, limit or liberalize its utilization. After reviewing the literature, it was concluded that metamizole should not be withdrawn from the countries where its use is still relatively free. However, metamizole causes life-threatening adverse events that are usually unpredictable and can only be prevented by better prescribing habits, so it is suggested that its use as a first-line agent should be restricted to the treatment of the pain of acute colic and circumstances in which parenteral administration of a non-narcotic agent is mandatory. Studies are needed to determine the role of second-line oral analgesics in terms of their overall toxicity and efficacy. In the meantime it is proposed that oral metamizole should be used only when other analgesics (e.g. paracetamol) have failed.

Reflex sympathetic imbalance. Response to epidural blockade.

Eleven patients (two male, nine female) were treated with epidural sympathetic blockade for reflex sympathetic imbalance, an incomplete manifestation of reflex sympathetic dystrophy. Each had developed severe pain, sensitivity, and disability disproportionate to associated trauma. One patient injured an ankle, and the remaining 10 patients one or both knees (12 knees). Seven patients had undergone previous surgery. All but one had a favorable response to initial blockade. This individual eventually failed treatment despite surgical sympathectomy. Seven have required readministration of a block for clinical relapse. Mean followup was 22 months (range, 10 to 41 months). Five underwent extensive psychological testing. All have required adjunctive forms of therapy including physical therapy, transcutaneous electrical nerve stimulation (TENS), antiinflammatory or other nonnarcotic agents. Recovery is typically prolonged, particularly if the diagnosis is delayed. Close attention to, and therefore prevention of, situations that trigger its recurrence is essential for successful rehabilitation.

Control of pain in cancer patients

Almost three quarters of patients with cancer have severe pain, from invasion of the cancer itself, from effects of therapy, or from causes unrelated to the cancer (but often exacerbated by it). With the proper pain-management strategy, however, pain can be controlled in most patients. The analgesic ladder for pain control, promoted by the World Health Organization, begins with a nonnarcotic agent, progresses to a weak narcotic plus a nonnarcotic, and finally reaches a strong narcotic. Adjuvant agents, which increase the analgesic potency of the drug being used, may be added at any level. The most common reasons for inadequate pain control in cancer patients are incorrect narcotic dosing and incorrect switching from one narcotic to another and from one route of administration to another. Factors that influence pain management (eg, fear, anxiety, sleep disturbance) should be treated as well with appropriate medications, behavioral therapy, counseling, hypnosis, and other supportive techniques. These points are illustrated in the case report (see box, page 328).

The evaluation of analgesic drugs. The case for experimental methods.

The current status of the experimental, as opposed to the traditional clinical, approach to the evaluation of analgesic activity is examined in the light of recent observations made with the submaximal tourniquet and electric shock methods of inducing experimental pain. The results obtained indicate that the submaximal effort tourniquet technique shows an acceptable degree of sensitivity in detecting the analgesic activity of both narcotic and non-narcotic agents which is not the case with the electric shock method. These differences in sensitivities between two different experimental methods are examined and some possible explanations offered for the findings. It is concluded that some modern experimental methods may now provide a valid and desirable alternative to the clinical approach for the evaluation of analgesic agents.

Analgesic activity of floctafenine after cholecystectomy

In a double-blind, crossover study involving 40 post-cholecystectomy patients, the analgesic activity of a new oral nonnarcotic agent, floctafenine, was compared with that of oral meperidine and oral propoxyphene. A behavioral approach to the measurement of pain relief, i.e., the measurement of pain on movement or coughing, was used in addition to the accepted subjective method. Floctafenine 200 mg was found to have analgesic activity intermediate between that of meperidine 75 mg and propoxyphene 65 mg. Patients reported the fewest side effects after floctafenine. Initial pain level was found to affect the final pain score. Effects on pain relief due to age, sex, time of the day, and carryover effects were also examined and not found to be significant.

Toxicological studies on floctafenine

The toxicity of floctafenine, a nonnarcotic agent with analgesic properties, was investigated in mice, rats, rabbits, and dogs after single-dose oral or parenteral administration, and in rats and dogs after repeated oral administration for periods of 6 months. At high doses, floctafenin induced gastric lesions, particularly in dogs. It has a safety margin between active dose and toxic dose much wider than that of aspirin or indomethacin. High doses administered to pregnant mice, rats, and rabbits had some embryotoxic, but no teratogenic activity.

Anti-nociceptive activity of clonixin in rhesus monkeys.

Clonixin (Sch 10304) [2-(2’ methyl-3’ chloro anilino) nicotinic acid] has been reported to be an orally effective analgesic and a non-steroidal anti-inflammatory agent in rodents (1). Clonixin has no dependence liability in monkeys (2) and its analgesic effect is not antagonized by naloxone in mice and rats (3). Clinical results with clonixin have shown degrees of analgesic effects not usually observed with non-narcotic agents. Single oral doses of clonixin ranging from 300–600 mg produced pain relief comparable to that seen with parenteral administration of morphine (4).

Anti-Nociceptive Activity of Clonixin in Rhesus Monkeys

Clonixin (Sch 10304) [2-(2’ methyl-3’ chloro anilino) nicotinic acid] has been reported to be an orally effective analgesic and a non-steroidal anti-inflammatory agent in rodents (1). Clonixin has no dependence liability in monkeys (2) and its analgesic effect is not antagonized by naloxone in mice and rats (3). Clinical results with clonixin have shown degrees of analgesic effects not usually observed with non-narcotic agents. Single oral doses of clonixin ranging from 300–600 mg produced pain relief comparable to that seen with parenteral administration of morphine (4).