Fentanyl in the Out-of-Hospital Setting: Variables Associated with Hypotension and Hypoxemia

doi:10.1016/j.jemermed.2009.02.009

The Journal of Emergency Medicine

Volume 40, Issue 2, February 2011, Pages 182-187

https://doi.org/10.1016/j.jemermed.2009.02.009 Get rights and content

Abstract

Background: Previous out-of-hospital fentanyl analgesia studies are limited by retrospective nature or low numbers. Study Objectives: This study sought to prospectively assess fentanyl safety in a large out-of-hospital group, to identify variables associated with post-fentanyl hypotension (HN; systolic blood pressure [SBP] < 90) or hypoxemia (HX; SpO₂ < 90%). Methods: As part of a new protocol requiring documentation of peri-dose vital signs and adverse effects associated with fentanyl bolus doses, our Emergency Medical Services helicopter service assessed 500 consecutive patients receiving fentanyl from July through September 2006. By a priori plan, we assessed HN and HX descriptively (median with interquartile range, exact confidence intervals [CIs]) and with multivariate regression. Results: In 1055 patients, post-fentanyl HN was noted 52 times (4.9%), being a continuation of pre-fentanyl HN in 24 patients (46.2%); HN was new in 28 patients (2.7% of 1055, 95% CI 1.8–3.8%). Regression showed no association between dependent variables HN (assessed for 1055 doses) or HX (528 doses in non-intubated) and independent variables age, diagnosis, gender, scene/inter-facility mission, dose, or total transport dose. Pre-and post-fentanyl SpO₂ means were unchanged: 98.8% (95% CI 98.5–98.9) vs. 98.6% (95% CI 98.3–99.0), respectively. Post-fentanyl HN was seen in patients with pre-fentanyl intubation (odds ratio [OR] 5.3, p = 0.002) and with pre-fentanyl low SBP (OR 40, p < 0.001). Conclusion: In a closely monitored out-of-hospital population, fentanyl incurs a low risk of significant hypoxemia. The risk of fentanyl-associated hypotension is also very low, but difficult to predict in the absence of acuity markers such as pre-existing hypotension.

Introduction

Alleviating pain in the pre-hospital setting improves patient comfort and promotes a more efficient transport and Emergency Department (ED) transition (1). Fentanyl is an ideal agent for prehospital analgesia due to its short-acting nature and safety profile (2, 3). Since its first use in the 1980s, multiple studies have demonstrated the safety of fentanyl in this environment (4, 5, 6, 7, 8). However, hypotension and hypoxemia remain potential concerns for any prehospital analgesic (9). Although recent work is characterized by better methodology, most studies that have assessed the question of fentanyl's prehospital safety are limited by retrospective design or low patient numbers (8). Furthermore, the prehospital literature continues to note concerns about use of fentanyl and other opioids due to the risk of hypotension or hypoxemia (9, 10, 11, 12, 13). We therefore sought to prospectively assess, in a large number of prehospital fentanyl administrations, the association between prehospital fentanyl administration and development of hypotension or hypoxemia.

This study's objectives were to assess for association between prehospital fentanyl administration and the occurrence of either of the following: hypotension, defined as a drop in systolic blood pressure (SBP) to below 90 mm Hg in a patient at least 5 years of age, or hypoxemia, defined as a drop in peripheral oxygen saturation (SpO₂) to below 90%.

The other aim of the study was to analyze cases in which fentanyl-associated vital sign abnormalities were noted. This analysis was performed to identify any factors that could be tested in future studies, for their predictive association with post-fentanyl hypotension or hypoxemia. Particular attention was focused on the characteristics of age, weight, gender, diagnosis, scene/inter-facility mission type, and dosage administered.

Section snippets

Materials and Methods

This institutional review board-approved prospective single-cohort study was conducted at an aeromedical transport service utilizing three helicopters, one fixed-wing jet, and a ground transport vehicle to transport patients to multiple urban tertiary centers.

Care for the study patients was provided by a nurse and paramedic crew, working with a protocol allowing for administration of bolus-dose fentanyl, with a maximum hourly dose of 5 μg/kg. In the year before the study's execution, the

Study Patients and Fentanyl Administrations

Of 500 patients, 99 (19.8%) were scene transports, 320 (64.0%) were male, and 232 (46.4%) were intubated either before or during transport (116 [23.2%] were intubated by critical care transport crew). A total of 432 (86.4%) patients were transported by helicopter, 10 (2.0%) by fixed-wing jet, and the remaining 58 (11.6%) patients by ground critical care transport. Diagnostic categories were: Trauma (n = 231, 46.2%), Cardiac (n = 85, 17.0%), Neurological (n = 66, 13.2%), and General

Discussion

Prehospital analgesia remains a priority for Emergency Medical Services (EMS) providers, and, in fact, pain relief represents an area of major potential impact for out-of-hospital practitioners (14). Many agents have been studied and found effective, but the opioids are generally the most commonly employed analgesics in the United States and elsewhere (14, 15, 16). Occasionally, agents such as nalbuphine and tramadol are reported to be useful in the field, and physician-staffed EMS units may

Limitations

This study has several limitations, in terms of both internal and external validity. Some internal validity issues include the reliance upon crew documentation, and the potential for missed fentanyl adverse effects. In a critically ill and injured population, untoward hemodynamic, respiratory, and other events are expected to occur regardless of appropriate medical treatment, and multiple therapies and interventions are provided simultaneously. Thus, it is difficult to attribute an adverse

Conclusion

Under close monitoring with assessment of vital signs at least every 5 min and continuous pulse oximetry, fentanyl analgesia is safe in the out-of-hospital setting. In this large group of critically ill, transported patients, analysis demonstrates that fentanyl incurs a near-zero risk of hypoxia. In addition, the risk of fentanyl-associated hypotension is also quite low, with associations demonstrated only between pre-existing hypotension and intubation (which may be interpreted as a marker for

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Cited by (16)

Re: Re: Transdermal fentanyl patch versus standard analgesia in postoperative oral submucous fibrosis patients: A triple blinded, randomised control trial
2023, British Journal of Oral and Maxillofacial Surgery
Pre-Hospital Administration of Opioids in Trauma Patients: Is Dose Associated With Outcomes?
2021, Journal of Surgical Research
Citation Excerpt :
Adequate control of pain is important in the management of trauma patients. While attempting to provide adequate pain control, side effects of opioids, such as sedation, hemodynamic deterioration, and respiratory depression, cannot be overlooked.3-5 In recent years, significant effort has been placed to create and implement standards for opiate prescription to mitigate these effects.6, 7
Opioids are commonly used as an analgesic agent in the prehospital setting. Current efforts to prevent and control prescription opioid overuse are focused on the in-hospital and post-discharge phases. The aim of our study was to assess the associations between pre-hospital opioids use and in-hospital outcomes among trauma patients.
We performed a 2 year (2016-2017) retrospective analysis of our Level-I trauma center database. We included all adult trauma patients (age > 18y) who received pre-hospital opioids (Fentanyl (F) or Morphine-Sulfate (MS)). Outcome measures were emergency-department (ED) hypotension (SPB < 90 mmHg), ED intubation, prescription opioid medication upon discharge, and mortality. Multivariate logistic regression was performed.
In total, 709 patients were included in the analysis. Cutoff values of 200 mcg F and 15 mg MS were significantly associated with adverse outcomes. Overall, the ED hypotension rate was 14.4%, ED intubation rate was 6%, and ED mortality rate was 3.1%. On regression analysis, higher dosages of both pre-hospital F and pre-hospital MS were independently associated with increased odds of ED hypotension, ED intubation, and discharge on opioid medications, but not with ED mortality.
Pre-hospital administration of high dose opioids is associated with increased odds of adverse outcomes. Collaborative efforts to standardize and control the overuse of opioids should target the pre-hospital setting to limit opioid associated adverse effects.
Development and Testing of a Novel Anaesthesia Induction/Ventilation Protocol for Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction
2018, Canadian Journal of Cardiology
Citation Excerpt :
In addition, fentanyl enhances cardioprotection via its antiarrhythmic activity, especially in arrhythmias associated with ischemia-reperfusion injury, and by inducing pharmacologic preconditioning of the myocardium.27 As expected, administration of fentanyl neither aggravated hemodynamics nor hampered the favourable effects of nasal cannula and NRFM on oxygenation.28 For the induction and paralysis, we administered midazolam 0.02 mg/kg, ketamine 0.35 mg/kg, 1% propofol 0.5 mg/kg slow I.V., and succinylcholine 0.8 mg/kg.
Cardiogenic shock is a life-threatening condition and patients might require rapid sequence induction (RSI) and mechanical ventilation. In this study, we evaluated a new RSI/mechanical ventilation protocol in patients with acute myocardial infarction complicated by cardiogenic shock.
We included consecutive adult patients who were transferred to the emergency department. The RSI protocol included 5 phases: preoxygenation, pretreatment, induction/paralysis, intubation, and mechanical ventilation (PPIIM). A posteriori, we selected historical patients managed with standard RSI as a control group. The primary outcome was hemodynamic derangement or hypoxemia from enrollment until intensive care unit (ICU) admission.
We studied 31 consecutive patients who were intubated using the PPIIM protocol and 22 historical controls. We found significant differences in systolic (85.32 ± 4.23 vs 71.72 ± 7.98 mm Hg; P < 0.0001), diastolic (58.84 ± 5.84 vs 39.05 ± 5.63 mm Hg; P < 0.0001), and mean arterial pressure (67.71 ± 4.90 vs 49.90 ± 5.66 mm Hg; P < 0.0001), as well as in partial pressure of oxygen (85.80 ± 19.82 vs 164.73 ± 43.07 mm Hg; P < 0.0001) between the PPIIM and control group at 5 minutes of automated ventilation. Also, statistically significant differences were observed in diastolic (59.74 ± 4.93 vs 47.86 ± 11.47 mm Hg; P < 0.0001) and mean arterial pressure (68.65 ± 4.10 vs 60.23 ± 11.67 mm Hg; P < 0.0001), as well as in partial pressure of oxygen (119.84 ± 50.57 vs 179.50 ± 42.17 mm Hg; P < 0.0001), and partial pressure of carbon dioxide (39.81 ± 10.60 vs 31.00 ± 9.30 mm Hg; P = 0.003) between the 2 groups at ICU admission. Compared with the control group, with PPIIM more patients survived to ICU admission (100% vs 77%) and hospital discharge (71% vs 31.8%), as well as at 90 days (51.6% vs 18.2%), and at 180 days (38.7% vs 13.6%).
The PPIIM protocol allows safe intubation of acute myocardial infarction patients with cardiogenic shock and improves hemodynamic and oxygenation parameters.
Le choc cardiogénique est une affection potentiellement mortelle pouvant nécessiter une intubation en séquence rapide (ISR) et une ventilation mécanique. Dans le cadre de cette étude, nous avons évalué un nouveau protocole d’ISR/de ventilation mécanique chez des patients ayant subi un infarctus aigu du myocarde compliqué par un choc cardiogénique.
Nous avons inclus des patients adultes consécutifs transférés dans un service d’urgence. Le protocole d’ISR comprenait 5 phases : préoxygénation, prétraitement, induction/paralysie, intubation et ventilation mécanique (PPIIVM). A posteriori, nous avons sélectionné des patients historiques pris en charge à l’aide d’une ISR standard à titre de groupe témoin. Le paramètre d’évaluation principal était le dérangement hémodynamique ou l’hypoxémie entre l’inscription et l’admission à l’unité des soins intensifs (USI).
Nous avons étudié 31 patients consécutifs intubés selon le protocole PPIIVM et 22 témoins historiques. Nous avons constaté des différences significatives au niveau de la pression systolique (85,32 ± 4,23 vs 71,72 ± 7,98 mm Hg; p < 0,0001), de la pression diastolique (58,84 ± 5,84 vs 39,05 ± 5,63 mm Hg; p < 0,0001) et de la pression artérielle moyenne (67,71 ± 4,90 vs 49,90 ± 5,66 mm Hg; p < 0,0001), mais également au niveau de la pression partielle de l’oxygène (85,80 ± 19,82 vs 164,73 ± 43,07 mm Hg; p < 0,0001) entre le groupe PPIIVM et le groupe témoin après 5 minutes de ventilation automatique. Des différences statistiquement significatives ont également été observées au niveau de la pression diastolique (59,74 ± 4,93 vs 47,86 ± 11,47 mm Hg; p < 0,0001) et de la pression artérielle moyenne (68,65 ± 4,10 vs 60,23 ± 11,67 mm Hg; p < 0,0001), ainsi qu’au niveau de la pression partielle d’oxygène (119,84 ± 50,57 vs 179,50 ± 42,17 mm Hg; p < 0,0001) et de la pression partielle de dioxyde de carbone (39,81 ± 10,60 vs 31,00 ± 9,30 mm Hg; p = 0,003) entre les deux groupes au moment de l’admission à l’USI. Comparativement au groupe témoin, les patients chez qui un protocole PPIIVM a été réalisé ont été plus nombreux à survivre à l’admission à l’USI (100 % vs 77 %) et à recevoir leur congé de l’hôpital (71 % vs 31,8 %). Ils étaient également plus nombreux à être en vie 90 jours (51,6 % vs 18,2 %) et 180 jours (38,7 % vs 13,6 %) après l’intervention.
Le protocole PPIIVM permet d’intuber en toute sécurité les patients ayant subi un infarctus aigu du myocarde qui présentent un choc cardiogénique, tout en améliorant les paramètres hémodynamiques et d’oxygénation.
Is pain really undertreated? Challenges of addressing pain in trauma patients during prehospital transport and trauma resuscitation
2016, Injury
Citation Excerpt :
Opioids like fentanyl and morphine have rapid onset, short half-life, adequate pain control, and no direct effect on increased bleeding risk [24,29,30]. Providers should strive for adequate pain relief, but must also maintain the ability to perform accurate assessment of injuries and prevent hypoxia or hypotension [19,24,29,31,34,36–38]. It is not unreasonable to be judicious in administering analgesia, especially for hypotensive or head injured patients [21,24,31].
Prior research has documented the inadequacy of pain management for trauma patients in the emergency department (ED), with rates of pain assessment and opioid administration averaging about 50%. Such rates, however, may be misleading and do not adequately capture the complexity of pain management practices in a trauma population. The goal of the study was to determine if pain was undertreated at the study hospital or if patient acuity explained the timing and occurrence of pain treatment in the prehospital setting and the ED.
A retrospective study was performed at a Level 1 adult trauma centre in the Midwest. The trauma registry was used to identify patients who received a trauma activation during the study period (June–November 2012; N = 313). Using the first set of patient vitals and ISS, patients were grouped into three categories: physiologically stable with low injury severity (n = 132); physiologically stable with moderate to severe injury (n = 122); and physiologically unstable with severe injury (n = 56). Differences were assessed with Kruskal–Wallis and chi-square tests.
Patients who were physiologically unstable were the least likely to receive a standardised pain assessment and the least likely to receive an opioid in the ED. Patients who were physiologically stable at entry to the ED but sustained a severe injury were the most likely to receive an opioid. Time to first pain assessment and time to first opioid did not differ by patient acuity.
Results confirm that patient acuity greatly affects the ability to effectively and appropriately manage pain in the initial hours after injury. This study contributes to the literature by noting areas for improvement but also in explaining why delaying pain treatment may be appropriate in certain patient populations.
Opioid analgesics and narcotic antagonists
2014, Side Effects of Drugs Annual
The Side Effects of Drugs Annuals form a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler’s Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the 2011 publications on adverse reactions to opioid analgesics and narcotic antagonists covers alfentanil, codeine, dextromethorphan, diamorphine (heroin), dihydrocodeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, papaverine, pethidine (meperidine), remifentanil, tramadol, buprenorphine, methylnaltrexone, and naltrexone. There is also a special review on takotsubo cardiomyopathy after opioid withdrawal.
The effectiveness and adverse events of morphine versus fentanyl on a physician-staffed helicopter
2012, Journal of Emergency Medicine
Citation Excerpt :
There is also the question of whether including fentanyl in prehospital formularies is worth the risk given its abuse potential among medical staff. Although surveillance data suggest that nationally, fentanyl is one of the least abused drugs in the non-physician population, fentanyl abuse by physicians is a well-recognized concern (24,25). Further research on this topic of prehospital opiate use could include a larger study powered to detect differences in adverse events between different opiates, as well as studies utilizing hydromorphone.
Morphine and fentanyl are both frequently used in prehospital trauma patients, but due to limited formulary size, we sought to study whether both drugs should be included.
The purpose of this study was to evaluate the effectiveness and safety of fentanyl as compared to morphine for patients requiring analgesic medications for a traumatic injury during transport via a physician-staffed air medical service.
Trauma patients were grouped by even and odd days (even - morphine 4 mg, odd - fentanyl 50 μg). Patients were excluded based on age (< 18 or > 64 years), hypotension, inability to communicate a pain score (intubated), or known allergy to the study drugs. During the flight, medical crew assessed numeric pain score, vital signs, and incidence of pruritis or nausea.
There were 103 patients enrolled in the morphine arm and 97 patients in the fentanyl arm. The mean pain score at the beginning of enrollment was 8.0 ± 2.0 in the morphine arm and 8.0 ± 1.8 in the fentanyl arm. The mean final pain score was 5.8 ± 2.7 in the morphine arm and 5.5 ± 2.4 in the fentanyl arm (n.s. by either t-test or non-parametric testing). There was no significant difference in analgesia between fentanyl and morphine. There were no significant differences in the incidence of pruritis or vomiting between the two groups. Average transport time was 37 ± 8 min in the morphine group, and 43 ± 11 min in the fentanyl group. Average number of morphine doses was 3 ± 1.2. For fentanyl, average number of doses was 3 ± 1.3.
In our study, there was not a significant difference in analgesic effectiveness between morphine and fentanyl. There was no significant difference in the incidence of adverse effects between the two drugs. Our study suggests that either drug can be used safely with equivalent effectiveness.

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Selected topic: Prehospital careFentanyl in the Out-of-Hospital Setting: Variables Associated with Hypotension and Hypoxemia

Abstract

Introduction

Section snippets

Materials and Methods

Study Patients and Fentanyl Administrations

Discussion

Limitations

Conclusion

J Emerg Med

Prehosp Emerg Care

Am J Emerg Med

Air Med J

Ann Emerg Med

J Am Coll Surg

Resuscitation

Am J Emerg Med

Prehosp Emerg Care

Prehosp Emerg Care

Ann Emerg Med

Burns

Ann Emerg Med

Ann Emerg Med

Fentanyl trauma analgesia use in air medical scene transports

J Emerg Med

Selected topic: Prehospital care
Fentanyl in the Out-of-Hospital Setting: Variables Associated with Hypotension and Hypoxemia