Postoperative complications with neuromuscular blocking drugs and/or reversal agents in obstructive sleep apnea patients: a systematic review.

BACKGROUND: Neuromuscular blocking drugs (NMBD) are administered intra-operatively to facilitate intubation and to achieve muscle relaxation for surgical procedures. Incomplete reversal of NMBD can lead to adverse events in the postoperative period. Patients with obstructive sleep apnea (OSA) may be at higher risk of complications related to the use of NMBD. The objectives of this systematic review were to determine whether: 1) OSA patients are at higher risk of postoperative complications from the use of NMBD than non-OSA patients, and 2) the choice of NMBD reversal agent affects the risk of postoperative complications in OSA patients. METHODS: A literature search of multiple databases was conducted up to April 2017. The inclusion criteria were: (1) adult surgical patients (≥18 years old) with OSA diagnosed by polysomnography, or history, or suspected by screening questionnaire; (2) patients who were given NMBD and/or NMBD reversal agents intraoperatively; (3) reports on postoperative adverse events, particularly respiratory events were available; (4) published studies were in English; and (5) RCTs or observational cohort studies. The quality of evidence was determined by the Oxford Center for Evidence Based Medicine levels of evidence. RESULTS: Out of 4123 studies, five studies (2 RCTs and 3 observational studies) including 1126 patients were deemed eligible. These studies were heterogeneous precluding a meta-analysis of the results. Two of three studies (1 RCT, 2 observational studies) reported that OSA patients given NMBD may be at higher risk of developing postoperative pulmonary complications (PPCs) like hypoxemia, residual neuromuscular blockade or respiratory failure compared to non-OSA patients. Two studies (1 RCT, 1 observational study) reported that OSA patients who were reversed with sugammadex vs. neostigmine had less PPCs and chest radiographic changes, but the quality of the included studies was Oxford level of evidence: low to moderate. CONCLUSIONS: OSA patients who receive intraoperative NMBD may be at higher risk for postoperative hypoxemia, respiratory failure and residual neuromuscular blockade compared to non-OSA patients. There is some, albeit very limited evidence that NMBD reversal with sugammadex may be associated with less PPCs than neostigmine in patients with OSA. More high-quality studies are needed.

Are There Pharmacotherapeutic Options for Underactive Bladder?

Currently, underactive bladder, the symptom-based correlate of the urodynamic diagnosis of detrusor underactivity, has no effective drug treatments. Use of sympathomimetics, targeting cholinergic receptors, is not supported by current evidence. Several potential targets are the subject of ongoing investigation.

Anticholinergic premedication to prevent bradycardia in combined spinal anesthesia and dexmedetomidine sedation: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: When dexmedetomidine is used in patients undergoing spinal anesthesia, high incidence of bradycardia in response to parasympathetic activation is reported. Therefore, we aimed to evaluate the effectiveness of atropine premedication for preventing the incidence of bradycardia and the hemodynamic effect on patients undergoing spinal anesthesia with sedation by dexmedetomidine. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Operating room. PATIENTS: One hundred fourteen patients (age range, 2-65 years; American Society of Anesthesiology class I-II) participated in this study, willing to be sedated and to undergo spinal anesthesia. INTERVENTION: The patients were divided into 2 groups: group A and group C. After performing spinal anesthesia, dexmedetomidine was infused at a loading dose of 0.6 µg/kg for 10 minutes, followed by an infusion at 0.25 µg/(kg h). Simultaneously with the loading dose of dexmedetomidine, patients in group A received an intravenous bolus of 0.5 mg atropine, whereas patients in group C received an intravenous normal saline bolus. MEASUREMENT: Data on administration of atropine and ephedrine were collected. Hemodynamic data including heart rate, systolic blood pressure, diastolic blood pressure (DBP), and mean blood pressure (MBP) were also recorded. MAIN RESULTS: The incidence of bradycardia requiring atropine treatment was significantly higher in group C than group A (P=.035). However, the incidence of hypotension needing ephedrine treatment showed no significant difference between the 2 groups (P=.7). Systolic blood pressure and heart rate showed no significant differences between the 2 groups (P=.138 and .464, respectively). However, group A showed significant increases in DBP and MBP, and group C did not (P=.014 and .008, respectively). CONCLUSION: Prophylactic atropine reduces the incidence of bradycardia in patients undergoing spinal anesthesia with dexmedetomidine sedation. However, DBP and MBP showed significant increases in patients when prophylactic atropine was administrated. Therefore, atropine premedication should be administered cautiously.

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

BACKGROUND: This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. OBJECTIVES: To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). SEARCH METHODS: For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. SELECTION CRITERIA: The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. DATA COLLECTION AND ANALYSIS: The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. MAIN RESULTS: In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. AUTHORS' CONCLUSIONS: There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

Effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on postoperative respiratory outcomes: a prospective study.

BACKGROUND: We tested the hypothesis that neostigmine reversal of neuromuscular blockade reduced the incidence of signs and symptoms of postoperative respiratory failure. METHODS: We enrolled 3,000 patients in this prospective, observer-blinded, observational study. We documented the intraoperative use of neuromuscular blocking agents and neostigmine. At postanesthesia care unit admission, we measured train-of-four ratio and documented the ratio of peripheral oxygen saturation to fraction of inspired oxygen (S/F). The primary outcome was oxygenation at postanesthesia care unit admission (S/F). Secondary outcomes included the incidence of postoperative atelectasis and postoperative hospital length of stay. Post hoc, we defined high-dose neostigmine as more than 60 µg/kg and unwarranted use of neostigmine as neostigmine administration in the absence of appropriate neuromuscular transmission monitoring. RESULTS: Neostigmine reversal did not improve S/F at postanesthesia care unit admission (164 [95% CI, 162 to 164] vs. 164 [161 to 164]) and was associated with an increased incidence of atelectasis (8.8% vs. 4.5%; odds ratio, 1.67 [1.07 to 2.59]). High-dose neostigmine was associated with longer time to postanesthesia care unit discharge readiness (176 min [165 to 188] vs. 157 min [153 to 160]) and longer postoperative hospital length of stay (2.9 days [2.7 to 3.2] vs. 2.8 days [2.8 to 2.9]). Unwarranted use of neostigmine (n = 492) was an independent predictor of pulmonary edema (odds ratio, 1.91 [1.21 to 3.00]) and reintubation (odds ratio, 3.68 [1.10 to 12.4]). CONCLUSIONS: Neostigmine reversal did not affect oxygenation but was associated with increased atelectasis. High-dose neostigmine or unwarranted use of neostigmine may translate to increased postoperative respiratory morbidity.

Reversal of rocuronium induced neuromuscular block with sugammadex or neostigmine: a large observational study.

BACKGROUND: This 'real-life' study aimed to analyze the time from the start of neostigmine or sugammadex administration to recovery to a train of four ratio (TOFr) of 0.9 in a real-life in patients receiving rocuronium. The secondary aims were to assess the proportion of patients: presenting TOFr < 0.9 after 5, 10, and 20 min from reversal agent administration, receiving opioids for intraoperative analgesia and extubated in the post-anesthesia care unit (PACU). METHODS: This was a multisite, prospective, nonrandomized, observational real-life study. Reversal agent was administered at either T2 reappearance or at a post-tetanic count of 1 or 2. Drugs dosages were free according to each investigator's usual practice. RESULTS: Three hundred fifty-nine patients were enrolled onto the study. Time from reversal administration to TOFr to 0.9 is significantly faster in the sugammadex group than in the neostigmine group (shallow block: 2.2 vs. 6.9 min, respectively; P < 0.0001; deep block: 2.7 vs. 16.2 min, respectively; P < 0.0001). The number of patients with TOFr < 0.9 at 5, 10, and 20 min post-reversal agent administration was higher in the neostigmine than in the sugammadex group. Just five patients did not receive opioids. All patients were extubated in the operative room except for a single patient in the sugammadex group who was extubated following PACU admission. CONCLUSIONS: This real-life study confirms that reversal time is faster in patients receiving sugammadex than in those receiving neostigmine. TOFr < 0.9 20 min after reversal was only present in patients treated with neostigmine.

Immediate cardiac arrest after neostigmine administration.

Many drugs used in anaesthesia have some potential fatal consequences; for example complete heart block and Q-Tc interval prolongation. Since the parasympathetic system in children is not fully developed, electrical transmission of the heart is not stable. Neostigmine is used in order to reverse neuromuscular block but it may also lead to prolongation of Q-Tc interval. We present a case of an 18-month-old male patient weighing 12kg subjected to a surgical operation because of congenital glaucoma. In order to reverse neuromuscular block at the end of operation, atropine and neostigmine were injected intravenously. However, cardiac arrest developed immediately after administration.

Application of umami taste stimulation to remedy hypogeusia based on reflex salivation.

Enjoying taste should be one of the greatest pleasures in human life. However, aging is sometimes associated with decreased taste sensitivity, also known as hypogeusia. The loss of taste not only affects quality of life, but can also cause weight loss and health problems in the elderly. Our recent study has shown that 37% of test subjects over 65 years of age exhibited hypogeusia. Further, whole saliva secretion, including minor salivary secretion, was significantly decreased in elderly patients with gustatory impairment, but was normal in all elderly subjects with normal taste thresholds. These data indicate that hyposalivation is closely related to hypogeusia. Moreover, clinical studies have shown that treatment of hyposalivation diminishes hypogeusia, indicating that salivation is essential to maintain normal taste function. However, many medications for relief of dry mouth, such as parasympathomimetic (cholinomimetic) drugs, have serious adverse effects. Palpitation, sweating, nausea, diarrhea and dizziness have all been observed in elderly patients taking parasympathomimetic drugs. To circumvent this problem, glutamate, which produces umami taste, was demonstrated to increase salivary secretion and thereby improve hypogeusia by enhancing the gustatory-salivary reflex. Our data suggests that umami is an effective tool for the relief of hypogeusia without the side effects of parasympathomimetic drugs.

Efficacy of bupivacaine-neostigmine and bupivacaine-tramadol in caudal block in pediatric inguinal herniorrhaphy.

BACKGROUND: Limited duration of analgesia is among the limitations of single caudal injection with local anesthetics. Therefore, the purpose of this study was to evaluate the effectiveness and safety of bupivacaine in combination with either neostigmine or tramadol for caudal block in children undergoing inguinal herniorrhaphy. METHODS: In a double-blinded randomized trial, sixty children undergoing inguinal herniorrhaphy were enrolled to receive a caudal block with either 0.25% bupivacaine (1 ml x kg(-1)) with neostigmine (2 microg x kg(-1)) (group BN) or tramadol (1 mg x kg(-1)) (group BT). Hemodynamic variables, pain and sedation scores, additional analgesic requirements, and side effects were compared between two groups. RESULTS: Duration of analgesia was longer in group BT (17.30 +/- 8.24 h) compared with group BN (13.98 +/- 10.03 h) (P = 0.03). Total consumption of rescue analgesic was significantly lower in group BT compared with group BN (P = 0.04). There were no significant differences in heart rate, mean arterial pressure, and oxygen saturation between groups. Adverse effects excluding the vomiting were not observed in any patients. CONCLUSION: In conclusion, tramadol (1 mg x kg(-1)) compared with neostigmine (2 microg x kg(-1)) might provide both prolonged duration of analgesia and extended time to first analgesic in caudal block.

Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed extract in rodent model of Parkinson's disease.

Mucuna pruriens (MP) has long been used in Indian traditional medicine as support in the treatment of Parkinson's disease. However, no systematic preclinical studies that aimed at evaluating the efficacy of this substance are available to date. This study undertook an extensive evaluation of the antiparkinsonian effects of an extract of MP seeds known to contain, among other components, 12.5% L: -dihydroxyphenylalanine (L: -DOPA), as compared to equivalent doses of L: -DOPA. Moreover, the neuroprotective efficacy of MP and its potential rewarding effects were evaluated. The results obtained reveal how an acute administration of MP extract at a dose of 16 mg/kg (containing 2 mg/kg of L: -DOPA) consistently antagonized the deficit in latency of step initiation and adjusting step induced by a unilateral 6-hydroxydopamine lesion, whereas L: -DOPA was equally effective only at the doses of 6 mg/kg. At the same dosage, MP significantly improved the placement of the forelimb in vibrissae-evoked forelimb placing, suggesting a significant antagonistic activity on both motor and sensory-motor deficits. The effects of MP extract were moreover investigated by means of the turning behavior test and in the induction of abnormal involuntary movements (AIMs) after either acute or subchronic administration. MP extract acutely induced a significantly higher contralateral turning behavior than L: -DOPA (6 mg/kg) when administered at a dose of 48 mg/kg containing 6 mg/kg of L: -DOPA. On subchronic administration, both MP extract (48 mg/kg) and L: -DOPA (6 mg/kg) induced sensitization of contralateral turning behavior; however, L: -DOPA alone induced a concomitant sensitization in AIMs suggesting that the dyskinetic potential of MP is lower than that of L: -DOPA. MP (48 mg/kg) was also effective in antagonizing tremulous jaw movements induced by tacrine, a validated test reproducing parkinsonian tremor. Furthermore, MP induced no compartment preference in the place preference test, indicating the lack of components characterized by rewarding effects in the extract. Finally, in a subchronic mice model of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced dopamine neuron degeneration, MP extract did not prove capable of preventing either tyrosine hydroxylase decrease induced by MPTP or astroglial or microglial activation as assessed by means of GFAP and CD11b immunohistochemistry, supporting the absence of neuroprotective effects by MP. Characterization MP extract strongly supports its antiparkinsonian activity.

A case of acute post-laparoscopy bowel hypermotility and treatment with hyoscine butylbromide.

Post-laparoscopic pain is multi-factorial and many modes of perioperative analgesia have been proposed. We present the case of a patient who experienced severe abdominal pain following gynaecologic laparoscopy. Repeat laparoscopy revealed small bowel hypermotiliy which was successfully treated with intravenous (i.v.) hyoscine butylbromide. Neostigmine, a widely used muscle relaxant reversal agent, is known to increase small bowel motility. Intravenous hyoscine butylbromide is a rapid treatment of neostigmine-induced small bowel hypermotility post-laparoscopy.

Less tachycardia in adults when using atropine 0.9 mg compared with 1.2 mg plus neostigmine 2.5 mg.

OBJECTIVE: Compare the increase in heart rate in adults after 0.9 vs. 1.2 mg of atropine plus neostigmine 2.5 mg as the non-depolarizing muscle relaxant reversal agent. MATERIAL AND METHOD: A randomized, double blind, controlled trial on 46 adults ASA I-II, undergoing elective gynecological or general surgery with balanced general anesthesia was performed. The subjects were randomized into two groups, After surgery, the study group received 0.9 mg of atropine, while the control group received 1.2 mg of atropine. Both groups received 2.5 mg of neostigmine simultaneously. RESULTS: The heart rate and blood pressure were taken at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, and 30 min after the injection. The increase in heart rate and blood pressure between the two groups were compared. The heart rate (at 3, 4, 5, and 6 min) of patients in the study group increased significantly less than that of patients in the control group. There was no significant difference in blood pressure between groups and no side effects occurred. CONCLUSION: The authors conclude that 0.9 mg of atropine with 2.5 mg neostigmine can be safely used as the reversal agent for a non-depolarizing muscle relaxant, particularly in patients for whom any increase in heart rate would be harmful.

[Ocular side effects of glaucoma treatment agents]. / Les effets secondaires des antiglaucomateux.

Antiglaucomatous ocular side effects can be divided into specific and non specific ones. Non specific ocular side effects are mainly caused by preservative agents; they are essentially external ocular irritations. Specific ocular side effects are strongly related to the mechanism of action of the drug. These specific ocular side effects are described, caution being taken to precise the strength of the association between each side effect and the related drug by using the classification of World Health Organisation (WHO) (certain, probable, possible or unlikely).

Adverse drug reactions during heatwaves.

Patients receiving the following drugs should be closely monitored during heatwaves: psychotropics, atropinics, amphetamine-like drugs, parasympathomimetic agents such as cholinesterase inhibitors, thyroid hormones, drugs that increase the risk of renal failure in case of dehydration, and betablockers.