Glycopyrrolate for drooling in children with medical complexity under three years of age

Background The aim of the study is to determine that Glycopirrolate is safe and effective in decreasing drooling in children with medical complexity under 3 years of age. Medical treatment is based on anticholinergic drugs as transdermal scopolamine, benzotropine and GLY. GLY (Glycopyrronium bromide) is a synthetic quaternary ammonium anticholinergic agent with poor blood–brain barrier penetration and consequently has limited central effects. Actually, the oral GLY formulation was approved by the United States Food and Drug Administration (FDA) to treat drooling in children aged 3–16 years. Five studies reported on GLY use for the treatment of drooling in children with cerebral palsy and other conditions with neurological impairment; four are prospective studies while one a retrospective review. Methods this is a case report of eighteen children (sex ratio 11/8, median age 17 months, range 2–36 months) under three years of age, followed by a multidisciplinary team at the Bambino Gesù Children Hospital. The median follow-up was of 31.5 months (range 1–69 months). Response to treatment was assessed according to the Drooling Impact Scale administered at time 0 and after 1 month. All patients have an important neurological impairment: nine patients have a cerebral palsy (Gross Motor Function Classification System class V) and nine a genetic/malformative syndrome. Twelve patients have a tracheostomy and two need mechanical ventilation. Gastrostomy is present in 16 out of 18 patients. All patients received Glycopirrolate. The median starting daily dose was 0.065 mg/kg/die (range 0.02–0.21 mg/kg/die) three times a day. The drooling impact scale was administered at time O and after 1 month. Results Four out 18 patients stopped treatment for adverse event, lack of efficacy or parental decision. The mean Drooling Impact Scale at time 0 was 89 (range 81–100) and after 1 month 61(range 43–78); the difference was statistically significant (P < 0.001). The overall response to treatment was 94%. Conclusions This is the first study to determine the safety and effectiveness of Glycopyrrolate in decreasing drooling in a specific subset of patients. No major side effects were observed. Further comparative studies are needed to confirm our results.

A case of delayed-onset multiple oculogyric crisis and torticollis episodes after low dose intramuscular haloperidol in a non-neuroleptic drug overdose setting

This report documents a rare case of delayed-onset multiple acute dystonias after treatment with low dose intramuscular (IM) haloperidol lactate injection in a setting of non-neuroleptic drug overdose. The drug–drug interactions between haloperidol and high levels of paracetamol and naproxen are deliberated upon. A 25-year-old Asian female was admitted after an intentional overdose of medications (paracetamol, naproxen and pregabalin). She received 5 mg of IM haloperidol injection for agitation. 21 hours later she experienced mild intermittent ocular deviation in an upward and outward direction and generalised stiffness, which were self-resolving. An hour later, she required another 2.5 mg of IM haloperidol injection for further agitation. In the 35 hours following her first IM haloperidol (13 hours after the second IM haloperidol), she developed a total of three episodes of oculogyric crisis (OGC) with torticollis. Each episode was treated promptly with IM diphenhydramine 25 mg, and there was remission of symptoms within 15 minutes of treatment. An objective causality assessment revealed a definite relationship between the episodes of acute dystonia with IM haloperidol therapy. Where oral alternatives and IM atypical antipsychotics/benzodiazepines are unavailable, rapid tranquillisation with a high-potency typical antipsychotic is a possibility. However, consideration should be made to combine haloperidol with an anticholinergic agent as prophylaxis against acute dystonia, especially in the setting of drug overdose, even if it is that of a non-neuroleptic drug (in this case, paracetamol and naproxen).

Penehyclidine mitigates postoperative nausea and vomiting and intraoperative oculocardiac reflex in patients undergoing strabismus surgery: a prospective, randomized, double-blind comparison

Background Postoperative nausea and vomiting (PONV) is one of the most frequent complications following strabismus surgery. Penehyclidine, an anticholinergic agent, is widely used as premedication. This study investigated the effect of preoperative penehyclidine on PONV in patients undergoing strabismus surgery. Methods In this prospective, randomized, double-blind study, patients scheduled for strabismus surgery under general anesthesia were randomly assigned to either penehyclidine (n = 114) or normal saline (n = 104) group. Penehyclidine was administrated immediately after anesthesia induction, and normal saline was substituted as control. PONV was investigated from 0 to 48 h after surgery. Intraoperative oculocardiac reflex (OCR) was also recorded. Results Compared with normal saline, penehyclidine significantly reduced PONV incidence (30.7% vs. 54.8%, P < 0.01) and mitigated PONV severity as indicated by severity scoring (P < 0.01). Compared with normal saline, penehyclidine also significantly reduced OCR incidence (57.9% vs. 77.9%, P < 0.01) and mitigated OCR severity, as indicated by the requirement for atropine rescue (77.3% vs. 90.1%, P < 0.05) and the maximum decrease of heart rate during OCR (23.1 ± 9.4 bpm vs. 27.3 ± 12.4 bpm, P < 0.05). The recovery course did not differ between groups. Conclusions Penehyclidine administrated after anesthesia induction significantly reduced the incidence of PONV and alleviated intraoperative OCR in patients undergoing strabismus surgery. Trial registration ClinicalTrials.gov (NCT04054479). Retrospectively registered August 13, 2019.

Glycopyrrolate for Drooling in Children with Medical Complexity Under Three Years of Age

Background: The aim of the study is to determine that Glycopirrolate is safe and effective in decreasing drooling in children with medical complexity under three years of age. Medical treatment is based on anticholinergic drugs as transdermal scopolamine, benzotropine and GLY. GLY (Glycopyrronium bromide) is a synthetic quaternary ammonium anticholinergic agent with poor blood–brain barrier penetration and consequently has limited central effects. Actually, the oral GLY formulation was approved by the United States Food and Drug Administration (FDA) to treat drooling in children aged 3-16 years. Five studies reported on GLY use for the treatment of drooling in children with cerebral palsy and other conditions with neurological impairment; four are prospective studies while one a retrospective review. Methods: this is a case report of eighteen children (sex ratio 11/8, median age 17 months, range 2-36 months) under three years of age, followed by a multidisciplinary team at the Bambino Gesù Children Hospital. The median follow-up was of 31.5 months (range 1-69 months). Response to treatment was assessed according to the Drooling Impact Scale administered at time 0 and after 1 month. All patients have an important neurological impairment: nine patients have a cerebral palsy (Gross Motor Function Classification System class V) and nine a genetic/malformative syndrome. Twelve patients have a tracheostomy and two need mechanical ventilation. Gastrostomy is present in 16 out of 18 patients. All patients received Glycopirrolate. The median starting daily dose was 0.065 mg/kg/die (range 0.02-0.21 mg/kg/die) three times a day. The drooling impact scale was administered at time O and after 1 month. Results: Four out 18 patients stopped treatment for adverse event, lack of efficacy or parental decision. The mean Drooling Impact Scale at time 0 was 89 (range 81-100) and after one month 61(range 43-78); the difference was statistically significant (P <0.001). The overall response to treatment was 94%. Conclusions: This is the first study to determine the safety and effectiveness of Glycopyrrolate in decreasing drooling in a specific subset of patients. No major side effects were observed. Further comparative studies are needed to confirm our results.

Prevalence, risk factors, and optimized management of moderate-to-severe thirst in the post-anesthesia care unit

Post-operative thirst is common and may cause intense patient discomfort. The aims of this retrospective study conducted in a high-volume post-anesthesia care unit (PACU) were as follows: (1) to examine the prevalence of moderate-to-severe post-operative thirst—defined as a numerical rating scale (NRS) score of 4 or higher, (2) to identify the main risk factors for moderate-to-severe post-operative thirst, and (3) to maximize the efficacy and safety of thirst management through a quality improvement program. During a 1-month quality improvement program conducted in August 2018, a total of 1211 adult patients admitted to our PACU were examined. Moderate-to-severe thirst was identified in 675 cases (55.8%). The use of glycopyrrolate during anesthesia was associated with moderate-to-severe thirst (71.7% versus 66.4%, respectively, p = 0.047; adjusted odds ratio: 1.46, p = 0.013). Following a safety assessment, ice cubes, room temperature water, or an oral moisturizer were offered to patients. A generalized estimating equation model revealed that ice cubes were the most effective means for thirst management—resulting in an estimated thirst intensity reduction of 0.93 NRS points at each 15-min interval assessment (p < 0.001)—followed by room temperature water (− 0.92/time-point, p < 0.001) and the oral moisturizer (− 0.60/time-point; p < 0.001). Patient satisfaction (rated from 1 [definitely dissatisfied] to 5 [very satisfied]) followed a similar pattern (ice cubes: 4.22 ± 0.58; room temperature water: 4.08 ± 0.55; oral moisturizer: 3.90 ± 0.55, p < 0.001). The use of glycopyrrolate—an anticholinergic agent that reduces salivary secretion—was the main independent risk factor for moderate-to-severe post-operative thirst. Our findings may provide clues towards an optimized management of thirst in the immediate post-operative period.

Validation of In-vitro Deposition of Emitted Dose Method for Simultaneous Estimation of Formoterol Fumarate and Glycopyrrolate in combined Dry Powder Inhaler Aerosol Pharmaceutical Dosage Form

Formoterol Fumarate and Glycopyrrolate Dry powder inhaler is combined aerosol dosage form. The label claim of this combined dosage form is 25 mcg of Glycopyrrolate and 6 mcg of Formoterol Fumarate per respicap. It is prescribed for treatment of Asthma and COPD. Formoterol Fumarate is anti asthmatic drug (Bronchodilator) and Glycopyrrolate is quaternary ammonium compounds which is Anticholinergic Drug. A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs while Glycopyrrolate blocks muscarinic receptors thus inhibiting cholinergic transmission. Glycopyrrolate is also known as Glycopyrronium Bromide, an Anticholinergic agent. It is used to inhibit salivation and excessive secretions of the respiratory tract preoperatively; reversal of neuromuscular blockade; control of upper airway secretions; and part of treatment for peptic ulcer. The present study aimed to Validate HPLC method for determination of Deposition of emitted dose of Formoterol Fumarate and Glycopyrrolate Analytes. This study covers Precision, Linearity, Accuracy, Robustness, Ruggedness, stability of analytical solution and Specificity. The chromatographic method uses a reversed phase column Purosphere star RP 18e (125 mm × 4.6 mm x 5 μm). The mobile phase was prepared by mixing Buffer : Acetonitrile : Methanol (68 : 24 : 8 %v/v/v) at flow rate 1.0 ml per min with UV and PDA detector 215 nm, column oven adjusted to 25° C with injection volume 100 μL. The method showed a successful application for determination of Formoterol Fumarate and Glycopyrrolate in Dry powder inhaler pharmaceutical formulation.

FORMULATION, DEVELOPMENT AND EVALUATION OF FAST DISSOLVING DRUG. LEVOSALBUTAMOL TABLETS

Asthma symptoms are the result of bronchial hyperresponsiveness, bronchospasm, and chronic airway inflammation. Short-acting, inhaled beta2 agonists; oxygen; intravenous fluids; and corticosteroids are the mainstays of treatment for acute exacerbations. The R-enantiomer of albuterol is responsible for bronchodilation. The S-enantiomer exhibits broncho-constricting activity in vitro, which may be mediated by muscarinic receptors and may be opposed by adding the anticholinergic agent ipratropium bromide. Levalbuterol improves pulmonary function to a greater extent than racemic albuterol and reduces the need for costly hospitalizations in patients with acute asthma exacerbations. It was estimated that more than 339 million people suffer from asthma. Asthma is the most common noncommunicable disease among children. Most deaths occur in older adults. Under Preformulation study, the physicochemical properties were complied with the IP and USP specification. Physical properties such as appearance, melting point, effect of temperature and humidity in different conditions were more in Levosabutamol raw powder. Parameters evaluated were within the USP limit. The compatibility evaluations were performed by FTIR spectroscopy. The observation implies that the drug and polymers were compatible with each other. There were no interaction found between polymers and drug. The formulations were evaluated on the basis of Pharmacopoeial specification visual appearance, pH, drug content, Hardness, Friability, Disintegration test, assessment of drug release, release kinetics were carried out as per specifications and results were found to be complied with the Pharmacopoeial specification.

Palliative care physicians’ perspectives of management for terminally ill cancer patients with death rattle: a nationwide survey

Death rattle occurs during the last days of life, and relatives of those afflicted frequently report that it is very distressful. However, there is no effective treatment for it. The purpose of this study was to investigate the perceptions of Japanese palliative care physicians in clinical practice in Japan. We conducted a nationwide survey of 268 physicians via an anonymous, self-report questionnaire. We assessed pharmacological and non-pharmacological management and anticholinergic agent choice. One hundred eighty-nine physicians (70.5%) returned the questionnaires. Fifty-five participants (29.1%) treating patients with Type-1 (real death rattle) and 36 participants (19%) treating patients with Type-2 (pseudo-death rattle) death rattle reported that they would frequently administer an anticholinergic agent. One-fourth would administer scopolamine butylbromide or scopolamine hydrobromide. In conclusion, more Japanese palliative care physicians thought that anticholinergic agents might be effective for treating Type-1 death rattle rather than Type-2. Further clinical trials of these agents are needed.