Nasal nalbuphine analgesia in prehospital trauma managed by first-responder personnel on ski slopes in Switzerland: an observational cohort study

Pain is one of the major prehospital symptoms and requires prompt management, in particular in trauma patients. Nevertheless, many colleagues report that analgesia in the field is insufficient for multiple reasons, one being the overly long response times of the emergency medical service (EMS) [1‐5]. In Switzerland, EMS units are staffed with ALS-qualified paramedics, but due to mountainous and alpine terrain, the time until arrival at the scene can be prolonged [6‐9]. Therefore, Switzerland also has a long history of helicopter emergency services (HEMS), staffed with a pilot, a paramedic and an ALS-qualified emergency physician. Usually, a given HEMS service can reach every point in Switzerland within 15 min, subject to weather conditions [10].

Winter sports such as downhill skiing and snowboarding attract > 2.5 million skiers annually in Switzerland, with about 76,000 injured skiers requiring treatment [11]. First responders in an accident on a ski slope are usually ski lift employees who provide first aid but no analgesia. However, providing analgesia on ski slopes may be achievable with nalbuphine due to its safety features (mixed agonist/antagonist), its ceiling effect regarding respiratory depression, an analgesic potency approximately 0.8 to 0.9 times that of morphine [12], its simple handling and legal approval, its lack of potential for abuse, its safety in pregnant and lactating women, and its potential for use by first responders [13‐16, 13, 17, 18].

There are several approved routes of nalbuphine administration, including intravenous (IV), intramuscular (IM), subcutaneous (SC) [13], and nasal, due to nalbuphine’s high lipophilicity and low molecular weight [17, 19‐21, 22‐24]. Because of its simplicity and non-invasive nature, we chose the nasal route for nalbuphine administration by ski slope first responders. Our hypothesis was that nasal nalbuphine would have no effect on pain in victims of ski slope accidents.

This observational cohort study examined data collected from patients given nalbuphine analgesia by first responders in the prehospital phase. Reporting of the study conforms to the STROBE statement for the reporting of observational cohort studies.

In our study, the majority of the patients reported a mean reduction of 3 points on the NRS, without any major adverse events, after nalbuphine administration.

The pain relief reported in our study is consistent with the literature, where a decrease of more than 2 points on the NRS was deemed good pain relief [25]. A study with out-of-hospital use of nasal fentanyl also showed an average reduction of 3 points on the NRS, leading to the conclusion that nasal fentanyl is effective for analgesia in the pre-hospital phase [26].

Only a few studies have evaluated analgesia with nalbuphine in the prehospital setting, and they had conflicting results. When given by paramedics out-of-hospital, IV or IM nalbuphine reduced pain by 5 points on the NRS [27], while the same strategy resulted in excessive morphine requirements after hospital admission in a case series. That study even reported less decline in pain scores after further administration of analgesics in the emergency department in prehospital nalbuphine patients [28], which is in accordance with a case review that described increased opioid requirements after nalbuphine [18]. In fact, this is expected because of the mixed agonist/antagonist effects of nalbuphine, with agonistic effects on the κ-receptors and antagonistic effects on the μ-receptor [12]. Therefore, if analgesia is continued with pure μ-receptor agonists, an increased dose is needed to overcome the antagonistic effect exerted by nalbuphine. Another possible disadvantage of mixed opioid agonist/antagonists is a limited analgesic effect or ceiling effect [12]. This could explain why no patient was completely free of pain after nalbuphine, with a minimum NRS of one after treatment. We did not find any significant differences between sexes regarding pain intensity before or after nalbuphine, regardless of the administered dose. There is some evidence that nalbuphine has a pain-facilitating effect in males, at least if it is administered in small doses of 5 mg [29], an effect we did not observe. There was a predominance of males in our study (58.8% vs. 41.2%) which is consistent with the average distribution of injured people on Swiss ski slopes (56.6% male vs. 43.4% female) [30]. We observed only a few minor side effects in our patients. Although unlikely, the risk of respiratory depression, monitored by pulse oximetry and respiratory rate, also exists following nalbuphine [12, 16, 17], but this was not reported in our study. Interestingly, in our study only 15% of trauma patients reported dissatisfaction with nalbuphine, and though the number of patients who reported a good analgesic effect was high (60.0%). This phenomenon was already described in labouring women treated with nalbuphine: only 54–57% of the parturient women experienced good pain relief, but 78% were willing to have the same treatment in a subsequent birth [15]. This could possibly be explained by a reported feeling of relaxation, rather than pain relief [15].

There is also evidence that satisfaction with opioid treatment seems to be influenced, at least in part, by rapid onset [16]. Nasally administered drugs are normally well absorbed, with rapid onset of action due to the rich blood supply and large surface of the mucosa, bypassing of a first-pass-effect and, maybe at least in part bypassing the blood-brain-barrier [21].

Our study has some limitations. First, we could not follow up patients after handover to EMS/HEMS personnel. Second, we mainly observed traumatic shoulder and knee injuries, which is expected with the predominance of our study sites being in Swiss ski resorts [30]. Third, there could be a bias in data collection because it was performed directly by first responders. If a patient felt sympathies for his rescuer, it is possible that the answers have been whitewashed, in particular regarding qualitative outcomes such as overall satisfaction. Fourth, although the qualitative pain reduction was reported for each patient, there were missing NRS values after nalbuphine in 10.5% (n = 28) of the patients, which is to be expected in an observational study in the pre-hospital setting. There was also a predominance of the male sex, which could have had an influence on the described pain reduction. We observed only a few minor side effects with nalbuphine. However, we did not follow up on the patients, and we cannot prove that nalbuphine administration is always safe.

In conclusion, nasal nalbuphine administered by first responders was a noninvasive pain management strategy that provided effective and presumably safe analgesia in prehospital, acutely injured patients in our studied environment. This method may provide an alternative, especially in situations involving severe pain and prolonged time between arrival of the first responders and arrival of EMS/HEMS personnel on scene. This conclusion is viable in the setting described, involving trained first responders. Further studies would be needed to include an overall recommendation for laypersons.