Analgesia and control of postoperative shivering
Retrospective study
Pathos 2025; 32.4. Online 2025, Nov 25
_________________________________________________________________________________
Nicola Maratea,1 Paolo Salomone 2
1 Head of UOSD
Coordination of Anaesthesia Activities
and Pain Therapy
2 Anaesthesia, Critical Care and Pain Management,
Policoro Hospital, ASM Matera, Italy
_________________________________________________________________________________
Summary
Nefopam hydrochloride was used to prevent and treat postoperative pain and shivering in 350 patients undergoing general anaesthesia (TIVA-TCI and ALR, including CSE, subarachnoid and epidural blocks) for general, gynaecological, orthopaedic and otolaryngological surgery. Disappearance of irregular oscillations due to tremor on the ECG trace, as well as clinical observation of the patient's condition, were used as indicators of the drug's efficacy. The efficacy of the treatment, the course of subjective symptoms, and the occurrence of any side effects were evaluated. In our experience, nefopam hydrochloride has proven effective in preventing shivering with minimal side effects. It exhibits various synergistic properties in the treatment of postoperative pain and shivering, without demonstrating synergy with anaesthetic drugs. No haemodynamic or sedative events were observed in any of the patients treated.
Riassunto
Il nefopam cloridrato è stato impiegato nella prevenzione e nel trattamento del dolore e del brivido postoperatorio in 350 pazienti sottoposti ad anestesia generale TIVA-TCI e ALR (CSE, subaracnoidea, peridurale, blocchi) per interventi di chirurgia generale, ginecologica, ortopedica e otorinolaringoiatrica. Come indice di efficacia del farmaco è stata utilizzata la scomparsa delle oscillazioni irregolari dovute al tremore sul tracciato ECG e l’osservazione clinica dell’andamento del fenomeno sul paziente. Sono stati valutati l’efficacia del trattamento, l’andamento della sintomatologia soggettiva e il rilievo degli eventuali effetti collaterali. Il nefopam cloridrato è risultato, nella nostra esperienza, dotato di efficace azione antibrivido, con scarsa incidenza di effetti collaterali. Esso assomma varie proprietà sinergiche nel dolore postoperatorio e nell’azione antibrivido, senza peraltro mostrare sinergismo con i farmaci dell’anestesia. Non sono stati osservati eventi avversi emodinamici o sedativi in tutti i pazienti trattati.
Key words
Pain, postoperative shivering, analgesia, nefopam
Parole chiave
Dolore, brivido postoperatorio, analgesia, nefopam
Introduction
The drugs used in anaesthesia alter normal thermoregulatory mechanisms at both the central and peripheral levels, resulting in significant heat loss, which is further accentuated when factors such as the microclimate of operating theatres also interfere.1,2 General and peripheral anaesthesia techniques induce significant vasodilation as a result of the ganglion block produced by anaesthetic drugs, and this, combined with the possible exposure of large areas of skin or viscera, can be responsible for heat loss, as highlighted by Lomax et al 3 and Borison et al.4 The body's need to maintain thermal homeostasis triggers mechanisms to compensate for heat loss, consisting of thermogenesis, the clinical expression of which is shivering.
Nefopam was developed in 1970 as an antidepressant and has long been used in the treatment of spasticity. In 1976, Gassel et al. 5 published a study demonstrating its powerful analgesic properties. Although its mechanism of action is not yet fully understood, this drug has proven to be an effective centrally acting (non-opioid) analgesic that inhibits the reuptake of noradrenaline, serotonin and dopamine.
It is generally considered a well-tolerated drug: the main side effects are nausea, vomiting, dry mouth and sweating; more serious, and much rarer, effects include tachycardia and mental confusion. Unlike NSAIDs, it does not affect platelet aggregation and does not cause respiratory depression, an effect seen with opioids. A meta-analysis by Evans et al 6 examined its efficacy and safety profile. Nine clinical studies were examined in which the drug was used orally and intravenously for the treatment of pain following major abdominal, gynaecological and orthopaedic surgery. In addition, several studies have highlighted its anti-shiver action without sedative effects (as is the case with clonidine). Postoperative shivering, in addition to being an unpleasant subjective sensation during the recovery phase from anaesthesia, can also cause serious complications, especially in patients with limited cardiorespiratory reserves. 7,8
Matherials and method
During 2025, the medical records of 350 patients with postoperative shivering after general anaesthesia, hospitalised between June 2016 and June 2024 in the departments of General Surgery, ENT, Obstetrics and Gynaecology, and Orthopaedics, were reviewed. General anaesthesia (TIVA, TCI) or local-regional anaesthesia (subarachnoid, epidural, CSE) was administered using:
Propofol as an intravenous anaesthetic
Sevoflurane as a volatile anaesthetic
Fentanyl and remifentanyl as analgesics
Rocuronium, cisatracurium, mivacarium as muscle relaxants
The clinical parameters considered were as follows:
Level of consciousness, fasciculations, trismus, diffuse contractures
and the instrumental parameters:
ECG, bloodless and bloody PA in 42 cases, SaPO2, entropy, NMT.
The protocol used was as follows:
When shivering appeared, 0.1 mg/kg of nefopam was administered intravenously over 30 seconds; this dose was repeated if the crisis had not disappeared after 5 minutes. Monitoring was maintained for 10 minutes after the end of the symptoms. Post-operative analgesia,7,8 was ensured by the use of a combination of paracetamol and nefopam according to the following schedule: 1 g paracetamol (10 mg/ml) pre-emptive analgesia and 1-2 vials of nefopam every eight hours to achieve an anti-shiver and analgesic effect.9
Results
Complete remission of clinical symptoms occurred within five minutes of the first administration in 248 of the cases treated; in the remaining 102 cases, a second administration was necessary, but the shivering disappeared within seven minutes in total. The symptoms began with fasciculations of the facial and neck muscles, followed by trismus and diffuse contractures. They regressed as spatial-temporal orientation and response to simple verbal stimuli were recovered. Two cases of vomiting occurred, but this regressed spontaneously after the nefopam bolus was administered. Monitoring of the ECG, blood pressure and SaPO₂ did not provide reliable data, as the shivering caused artefacts in the readings in some cases.
Discussion
Among the drugs used in the treatment of shivering, 10,11 many are burdened with considerable and multiple side effects, such as excessive sedation, hypotension, insomnia, irritability, lack of cooperation on the part of the patient and sometimes even respiratory depression. This, combined with possible synergism with anaesthetics, means that these drugs are far from being the “ideal” drug for resolving post-operative shivering.
Compared to the drugs used previously, nefopam hydrochloride, at the doses used in our experience, patients received 0.1 mg/kg intravenous nefopam hydrochloride diluted in physiological solution, and shivering upon awakening was treated with 0.15 mg/kg intravenous nefopam, seems to have two significant advantages: effective anti-shivering action and low incidence of side effects.
The prophylactic use of nefopam may be reserved for patients with cardiorespiratory reserves limited by age or concomitant diseases, in whom a calm and sometimes delayed awakening is preferable to the possible onset of serious complications secondary to the involuntary and severe stress represented by intense shivering.12
L’impiego terapeutico è consigliabile per la prontezza d’azione del farmaco, in tutti i pazienti sottoposti ad anestesia generale (TIVA-TCI) o loco-regionale (subaracnoidea- epidurale - CSE) che sviluppano brivido, anche a costo di un modesto prolungamento della permanenza presso il reparto operatorio.
Conclusion
The drug's rapid onset of action makes it suitable for therapeutic use in all patients undergoing general anaesthesia (TIVA-TCI) or local-regional anaesthesia (subarachnoid-epidural — CSE), even if it slightly prolongs their stay in the operating theatre.
Conflict of interests
the authors declare that the article was written without any conflict of interest.
Open Access-license (CC BY-NC 4.0)
Read Non-Commercial license
Published
25th November 2025
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