Recurrent Persistent Hiccups on Opioid Treatment: A Case Report and Literature Review

Figures & data

Table 1. Characteristics of opioid-related hiccup in the present case, whilst the patient was followed at our outpatient clinic.

Age (years)/Sex/Comorbidities	Dates	Opioid (dose) /indication	Persistent hiccup onset	Other ongoing treatments	Attempted hiccup treatments/effect	Discontinuation or rotation	Time to hiccup resolution (after opioid discontinuation or rotation)
64/male /polymetastatic clear cell renal cell carcinoma, arterial hypertension, obstructive sleep apnea syndrome, hiatal hernia with gastroesophageal reflux disease	May 2021	Oral hydromorphone (1.3 mg/4h) /painful secondary osteolytic lesions	Less than 4 hours after hydromorphone initiation (no previous titration with lower dose)	Metoprolol 75 mg daily, pantoprazole 20 mg daily, folic acid 5 mg daily, vitamin D3 800 UI daily, herbal supplements (Spirulina and Echinacea, unknown doses)	Haloperidol 0.5 mg QID /hiccup suppression at night	Hydromorphone discontinuation and oral baclofen 5 mg TID for 1.5 days	7 days
	January 2022	Subcutaneous fentanyl pump (100 µg/h) /painful secondary osteolytic lesions	No hiccup onset after cautious titration over 3 weeks	Metoprolol 75 mg daily, prednisone 20 mg daily, pantoprazole 20 mg daily, mirtazapine 30 mg daily, vitamin D3 800 UI daily, herbal supplements (Spirulina and Echinacea, unknown doses)	–	–	–

Figure 1. Graphic timeline of opioid treatments, hiccup occurrence, and management.

Table 2. Characteristics of opioid-related hiccup case reports in literature.

No.	Case report	Age (years) /Sex /Comorbidities	Opioid (dose) /indication	Persistent hiccup onset	Other ongoing treatments	Attempted hiccup treatments /effect	Discontinuation or rotation	Time to hiccup resolution (after opioid discontinuation or rotation)
1.	Lauterbach, E. C. (1999) (24)	55 /male /depression, generalized anxiety disorder, atrial fibrillation	Oral hydrocodone (5 mg/4h) /dental procedure	1 hour after hydrocodone initiation (no previous titration with lower dose)	Sertraline 100 mg daily, bupropion 100 mg daily, trazodone 100 mg daily, flurazepam 15 mg daily, digoxin 0.25 mg daily, warfarin 5 mg daily. Penicillin 500 mg QID was introduced at the same time as hydrocodone	Oral flurazepam, additional 15 mg at bedtime /hiccup suppression at night	Hydrocodone discontinuation	The night after discontinuation
2.	Wilcox, S. K. (2005) (21)	63 /male /squamous cell carcinoma of the right tonsil, no further detail reported	Oral slow release morphine (30 mg BID) /increasing pain on the right side of the neck, radiating into tongue and throat	1 hour after slow release morphine initiation, preceded by normal release morphine titration (unknown duration and dose)	Ferrous sulfate, pilocarpine, allopurinol and pancreatic enzymes (doses not reported). Paracetamol 1 g QID	None	Morphine discontinuation. After hiccup resolution, rotation to transdermal fentanyl patch 125 µ/h and oral oxycodone 10 mg as needed was well tolerated	48 hours
3.	Panchal, R. et al (2018) (25)	61 /male /diabetes mellitus since the age of 20, no further detail reported	IV tramadol (100 mg/12h) /lower limb cellulitis	1 hour after tramadol initiation (no previous titration with lower dose)	Usual treatment unknown. IV amoxicillin 1.2 g/8h and IV omeprazole 20 mg/12h and SC rapid insulin 4 IU once, were introduced at the same time as tramadol	Switch to oral tramadol 50 mg BID /persisting hiccup	Tramadol discontinuation and oral baclofen 10 mg TID for 3 days	3 hours
4.		60 /male /not reported	Oral tramadol (100 mg/24h) /lower limb cellulitis	2 hours after tramadol initiation (no previous titration with lower dose)	Usual treatment unknown. IV cefoperazone-sulbactam 1.5 g/12h, IV ciprofloxacin 400 mg/12h, IV pantoprazole 40 mg/24h, IV furosemide 40 mg/12h, SC rapid insulin 6 IU, and oral lactulose sirup 10% 20 ml/8h were introduced at the same time as tramadol.	Non-pharmacological measures /persisting hiccup	Tramadol discontinuation, IV metoclopramide 10 mg/12h and oral baclofen 10 mg/8h for 3 days	Unspecified
5.	Ruan, X. et al (2007) (26)	65 /female /no significant past medical history	Intrathecal morphine infusion pump (1.0 mg/24h) /degenerative lumbar disk disease, lumbar spinal stenosis, and lumbar radiculitis	12 hours after the intrathecal pump implantation, preceded by a 7 days outpatient controlled continuous epidural morphine pump trial	Slow-release morphine 30 mg TID, oxycodone/acetaminophen 10 mg/325 mg TID as needed, gabapentin 800 mg TID, tizanidine 4 mg BID, meloxicam 7.5 mg BID	Oral chlorpromazine as needed (unknown dose) /hiccup suppression at night, increased interval between hiccup bursts	Rotation from intrathecal morphine to intrathecal hydromorphone (0.3 mg/day)	16 hours
6.	Loomba, V. et al (2012) (27)	44 /male /not reported	Intrathecal morphine infusion pump (1.493 mg/24h) /complex regional pain syndrome of bilateral upper extremities	12 hours after the intrathecal pump implantation, preceded by a 24 h-long titration	Not reported	Oral baclofen 10 mg TID /persisting hiccup	Rotation from intrathecal morphine to intrathecal hydromorphone (0.481 mg/24h)	12 hours

Table 3. Frequency of hiccup reports for different opioids in VigiBase as of 04.14.2022.

Opioid	Total reports of potential side effects	Hiccup reports	Hiccup reports/total reports (%)
Morphine	138,395	70	0.051
Hydromorphone	68,754	18	0.026
Oxycodone	185,026	61	0.033
Hydrocodone	43,492	0	0.000
Codeine	18,776	8	0.043
Buprenorphine	98,667	28	0.028
Tramadol	170,070	124	0.073
Fentanyl	206,177	67	0.032

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