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 reported pain relief in our study is consistent with the literature, where a decrease of more than 2 points on the NRS was deemed a good pain relief after (22). A study with out-of-hospital use of nasal Fentanyl showed also an average reduction of 3 points on the NRS, concluding that nasal Fentanyl is effective for analgesia in the pre-hospital phase (23). Only few studies evaluated analgesia with Nalbuphine in the prehospital setting, however with conflicting results. When given by paramedics out-of-hospital, IV or IM Nalbuphine reduced pain by 5 points on the NRS (24), 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 (25), which is in accordance with a case review that described increased opioid requirements after Nalbuphine (15). In fact, this is expected because the mixed agonist / antagonist effects of Nalbuphine, with agonistic effects on the κ-receptors and antagonistic effects on the µ-receptor (9). Therefore, if analgesia is continued with pure µ-receptor agonists, an increased dose is needed to overcome the antagonistic effect exerted by Nalbuphine. Our study could not follow up patients after hand-over to EMS / HEMS personnel. Another possible disadvantage of mixed opioid agonist / antagonists is a limited analgesic effect or ceiling effect (9). This could explain that no patient was completely free of pain after Nalbuphine with a minimal NRS of one after treatment.
We did not find any significant differences between genders 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 (26), 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) (27). We observed only a few minor side effects. Although unlikely, the risk of respiratory depression exists also following Nalbuphine (9) (13) (14), but this was not reported in our study. Interestingly, in our study only 15% reported a bad satisfaction with Nalbuphine even 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 (12). This could possibly be explained by a reported feeling of relaxation, more than pain relief (12). There is also evidence that satisfaction with opioid treatment seems to be influenced, at least in part, by a rapid onset (13). Nasally administered drugs are normally well absorbed and show a 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 (18).
Our study has some limitations. We mainly observed traumatic shoulder and knee injuries, which is expected with the predominance of our study sites being in Swiss ski resorts (27). There could be a bias in data collection because it was performed directly by FR. 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. Although the qualitative pain reduction from each patient was reported, there were missing NRS values after Nalbuphine 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 gender; this 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 the patients, and we cannot prove that Nalbuphine administration is always safe.