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Original research
Ketamine decreased opiate use in US military combat operations from 2010 to 2019
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  1. Sally L Westcott1,2,
  2. A Wojahn1,3,
  3. T C Morrison1 and
  4. E Leslie1,4
  1. 1 Emergency Department, Combat Trauma Research Group, NMCSD, San Diego, California, USA
  2. 2 Emergency Department, Naval Hospital Guam, Agana Heights, Guam
  3. 3 Shock Trauma Platoon, Combat Logistics Battalion 13, 13th Marine Expeditionary Unit, Marine Corps Base Camp Pendleton, Camp Pendleton, California, USA
  4. 4 1st Medical Battalion, 1st Marine Logistics Group, 1st Marine Expeditionary Unit, Marine Corps Base Camp Pendleton, Camp Pendleton, California, USA
  1. Correspondence to Dr Sally L Westcott; slmwestcott{at}gmail.com

Abstract

Background Ketamine is a dissociative anaesthetic currently used in a variety of healthcare applications. Effects are dose dependent and cause escalating levels of euphoria, analgesia, dissociation and amnesia. Ketamine can be given via intravenous, intramuscular, nasal, oral and aerosolised routes. A 2012 memorandum and the 2014 Tactical Combat Casualty Care (TCCC) guidelines included ketamine as part of the ‘Triple Option’ for analgesia. This study investigated the effect of ketamine adoption by the US military TCCC guidelines on opioid use between 2010 and 2019.

Methods This was a retrospective review of deidentified Department of Defense Trauma Registry data. The study was approved by the Institutional Review Board of Naval Medical Center San Diego (NMCSD) and facilitated by a data sharing agreement between NMCSD and the Defense Health Agency. Patient encounters from all US military operations from January 2010 to December 2019 were queried. All administrations of any pain medications via any route were included.

Results 5965 patients with a total of 8607 pain medication administrations were included. Between 2010 and 2019, the yearly percentage of ketamine administrations rose from 14.2% to 52.6% (p<0.001). The percentage of opioid administrations decreased from 85.8% to 47.4% (p<0.001). Among the 4104 patients who received a single dose of pain medication, the mean Injury Severity Score for those who received ketamine was higher than for those who received an opioid (mean=13.1 vs 9.8, p<0.001).

Conclusion Military opioid use declined as ketamine use increased over 10 years of combat. Ketamine is generally used first for more severely injured patients and has increasingly been employed by the US military as the primary analgesic for combat casualties.

  • pain management
  • trauma management
  • accident & emergency medicine

Data availability statement

Data may be obtained from a third party and are not publicly available. Data were obtained through a data sharing agreement (DSA) with the Joint Trauma System (JTS) through the Defense Health Agency and are only available to those listed on the DSA.

https://doi.org/10.1136/military-2022-002291

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    WHAT IS ALREADY KNOWN ON THIS TOPIC

    • Ketamine has been studied as an alternative to opioids for acute pain management and has been incorporated into pain treatment protocols in some prehospital and emergency department environments.

    WHAT THIS STUDY ADDS

    • This study evaluated the effect of ketamine use as part of the military Tactical Combat Casualty Care protocol for acute traumatic pain on opioid administrations during a 10-year period.

    HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

    • The results of this study show that opioid use declined during the time period as ketamine use increased and support the use of ketamine as an opioid-sparing pain treatment.

    Introduction

    Since its first use in 1965, ketamine has become a versatile medication used for pain control, procedural sedation, induction and even psychiatric disease.1–3 Ketamine has few side effects which are generally dose dependent and uncommon (reported incidence of laryngospasm 0.07%–0.4%, reported incidence of emergence reactions 12%).4 5 The analgesic properties of ketamine have been studied extensively and are considered comparable to opiate therapy. Ketamine has been shown to be superior to morphine in several head-to-head comparisons.2 6–8 Overdoses of ketamine are considered generally benign, even after 100 times the standard effective dose.5 Additionally, ketamine use has been associated with lower incidences of post-traumatic stress disorder when given to service members to manage acute pain.9 Ketamine is considered a safe medication with large therapeutic and toxicological indices and has proven utility for a variety of clinical applications, particularly acute pain management.

    While opioids remain the most commonly used analgesics in prehospital and austere environments, their use can be associated with respiratory depression, excessive sedation, nausea and hypotension.10 11 On the battlefield, massive haemorrhage remains the most common cause of preventable death and using analgesia that potentially worsens hypotension is undesirable.12 Additionally, the potential for opioid addiction remains a serious concern.13 Throughout the ongoing US opioid epidemic, opioid use has been heavily scrutinised and attempts to limit their use have been initiated across the USA particularly in the prehospital and emergency department settings.14 15

    Because of its versatility, safety, favourable side effect profile and potential use as an opioid alternative, ketamine has been incorporated into both civilian and military prehospital pain treatment protocols in recent years. Studies of ketamine’s efficacy as a pain management modality in the prehospital environment have shown it to be equivalent or superior to opioids and would suggest ketamine could decrease opioid use.16 17 Ketamine use in the US military was established in a 2012 Tactical Combat Casualty Care (TCCC) memorandum and formalised in the 2014 TCCC update. Prior studies have demonstrated increased ketamine usage rates by military medical personnel following updates of TCCC guidelines but only one previous small study has sought to evaluate the subsequent effect on opioid use.18 19 This study aimed to assess the effect of ketamine adoption on opioid usage in all US combat operations over a 10-year period and to demonstrate an opioid-sparing effect of ketamine protocols.

    Methods

    This was a retrospective chart review of deidentified casualty data from January 2010 to December 2019. Data were obtained from the Joint Trauma System (JTS) through the Department of Defense Trauma Registry (DoDTR) database. The DoDTR database is an electronic database which comprised healthcare data for all trauma patients treated at a military Role II or higher medical treatment facility and is a consolidation of original paper and electronic records from every stage in a casualty’s care. Information for the study was requested from the JTS via a data sharing agreement and was extracted from the database by an unbiased third-party JTS-trained consultant who was blinded to the study’s aims. Entries were deidentified and assigned a random identification number prior to being assimilated into an Excel data sheet. This was done by the JTS prior to the authors receiving the data set.

    All patients who received any form of pain medication at least once during military combat operations over the 10-year period were included in the data set. This included in-the-field, prehospital, transport and facility-based data. Only records that lacked any pain medication administrations were to be excluded from the final analysis; however, there were no entries which met this exclusion criterion. Records with missing data points were excluded from final calculations involving the missing variables. Data were reviewed by a single reviewer. One-way analysis of variance was used to calculate group means. SPSS version 28 was used for statistical analysis.20

    Results

    Between 2010 and 2019, analgesia was administered 8607 times to a total of 5965 patients. The majority of patients were male (5839/5695, 97.9%) between the ages of 18 and 37 years (5333/5695, 93.6%). About half of the patients were US military members (2931/5695, 51.5%). Humanitarians, non-North Atlantic Treaty Organization (NATO) military and NATO military members made up the next largest cohorts of patients (table 1). Three-quarters of patients were injured during Operation Enduring Freedom (4546/5695, 76.2%). Cases from 2010 to 2011 constituted almost half of the total patients (2607/5695, 43.7%). Only 2.4% of patients died during the time frame analysed (145/5965).

    View this table:
    Table 1

    Combatant status of patients with breakdown by US military branch

    Most injuries occurred during battle and were classified as penetrating injuries (4137/5965, 69.4%). The majority of injuries were sustained from explosives (2151/5695, 36.1%), gunshot wounds (1772/5695, 29.7%) or improvised explosive devices (IEDs) (803/5695, 13.5%) (table 2). Data came primarily from Role III medical facilities (4479/5695, 75.1%). Approximately one-quarter of documented pain medication administrations were performed during transport (2048/8607, 23.8%). A small per cent of administrations were performed at the point of injury or battalion aid station (1463/8607, 17.0%).

    View this table:
    Table 2

    Number of patients with each type of injury

    Overall, there were 1883 administrations of ketamine and 6724 administrations of opioids. Information on the specific type of pain medication administered was missing for 48 patients (48/5695, 0.8%). The most common opioid administered was fentanyl (3194/8607, 37.1%), followed closely by morphine (2955/8607, 34.3%) (table 3). In 2010, ketamine was the pain medication of choice only 14.2% of the time (227/1598). By 2019, the absolute number of administrations of ketamine surpassed opioids and ketamine was administered 52.6% of the time (317/603) (figures 1 and 2). Over half of all pain medication administrations were via intravenous route (4611/8607, 53.6% total; 1029/1883, 54.6% for ketamine; 3582/6724, 53.3% for opioids). Ketamine was administered via the intramuscular route 15.7% of the time (296/1883) while only 7.4% of opioid administrations were intramuscular (498/6724). Opioids were also given orally in 10.1% of cases (680/6724).

    View this table:
    Table 3

    Opioid administrations broken down by type

    Figure 1
    Figure 1

    Ketamine versus opioid administration percentage by year.

    Figure 2
    Figure 2

    Ketamine versus opioid administration number by year.

    For patients who received a single dose of pain medication, ketamine use was associated with a significantly higher Injury Severity Score (ISS) versus those who received an opioid (mean=13.1 vs 9.8, p<0.001).

    The 1859 patients who received multiple doses of pain medication had a statistically higher ISS than the 4105 patients who only received medication a single time (14.0 vs 10.5, p<0.001). More than half of all pain medication administrations were given to the group that required multiple doses (4502/8607, 52.3%). Three-quarters of the medications administered to the multiple-dose group were opioids.

    Discussion

    Originally published in 1996, TCCC guidelines arose from observed injury patterns in military conflicts and provided an evidence-based approach to casualty care.21 The Committee on TCCC within the JTS oversees the development of the TCCC guidelines which have expanded from their original use in the special operations community to use by the entirety of the Department of Defense as the standard for battlefield medical care.22 Effective prehospital analgesia is a crucial component of TCCC guidelines and is emphasised in standardised trauma training received by military personnel.23 24

    The data suggest that the adoption of ketamine as the analgesic of choice was likely a result of TCCC guideline changes as has been suggested previously.25 Figures 1 and 2 demonstrate a sustained increase in proportional ketamine use after the 2012 TCCC memorandum and 2014 formal TCCC update, though it took almost 5 years for ketamine to become the dominant pain medication in theatre. The recommendation for ketamine use in patients with haemodynamic instability and the high ISS of the patients receiving ketamine in this study could explain part of its rise in use. The ability to give ketamine intramuscularly (296/1883, 15.7% of total ketamine administrations), its portability and shelf stability and its utility as both an analgesic and sedative have made it an attractive option for combat medics. Ultimately, ketamine’s increased use suggests that institutional guidelines can profoundly affect practice patterns—after being made available by TCCC guidelines, ketamine became the preferred analgesic in combat.

    There was a significant decrease in absolute analgesic use over the 10-year period of combat, likely owing to decreased kinetic activity and overall military footprint.26 In 2010, absolute and proportional rates of opioid use were high (1371/1598, 85.8%). However, as the decade of conflict progressed, proportional use of ketamine increased while that of opioids decreased. By 2019, ketamine became the analgesic of choice and overtook opioid usage (52.6% vs 47.3%). Interestingly, morphine demonstrated persistent use despite being dropped from the TCCC guidelines in 2014.22 23 A potential explanation for the continued use of morphine is the location of administration. The majority of administrations occurred at a Role III facility, also known as combat surgical hospitals, which represent the highest level of care within an area of military operations. Role III facilities were staffed to provide surgical and critical care with advanced providers functioning beyond TCCC guidelines and it was likely that a more comprehensive formulary was available. After 2014, fentanyl was the primary opioid administered perhaps in part because it was available in oral form which may have been more easily administered by providers in the field (680/6724, 10.1% of total opioid administrations).

    Despite continued opioid use and a decrease in analgesic administrations overall, the proportional decrease in opioid use over the study period suggests that ketamine is a viable pain medication alternative with an opioid-sparing effect. This study demonstrated that the rate of opioid administration was cut almost in half after the introduction of ketamine into pain treatment protocols. The potential impact this could have on opioid use in the USA is profound. As the opioid epidemic continues to plague the USA, efforts to limit the use of opioids focusing on provider education, monitoring programmes and abuse-deterrent medications have made limited headway in reducing opioid abuse and use disorder.14 27 However, between 100 and 125 million Americans continue to suffer from acute and chronic pain annually and effective opioid alternatives for the management of pain could represent the best long-term solution for controlling the epidemic.14 28 This study suggests that ketamine could be such a solution.

    Limitations

    This study is limited in that it only included patients who received pain medication and does not include all casualties during the study period. Previous studies have shown a casualty count of 8225 for a similar time frame (2008–2017) so it is possible that this study reflects a large percentage of the total casualties.29 However, conclusions about changes in battle injury patterns or trends over the 10 years of combat are not possible with this data set as it is not reflective of all patients during the time frame.

    Additionally, this study relies on battlefield medical records and has multiple omitted entries due to the nature of combat medicine. The timeline of pain medication administration and resultant vital sign abnormalities, procedures and subsequent pain medication administrations are unreliable and frequently incomplete. The retrospective observational design of this study as well as the data fidelity limitations makes head-to-head outcome-based analyses between ketamine and opioids difficult and likely inaccurate using this data set.

    Information on the training level for the care providers was unavailable due to significant gaps in the data. Medic and provider training has stressed attention to TCCC Card documentation (Department of Defense [DOD] form 1380) and subsequent data fidelity is likely to increase in future studies.

    Conclusion

    In the years 2010–2019, ketamine was increasingly adopted by the US military. Considering decreasing rates of kinetic battlefield activity, this study demonstrated an increase in proportional ketamine use relative to opioids. By 2019, rates of ketamine use surpassed that of opioids by military medics and providers. Increases in ketamine use were associated with TCCC guideline revisions and demonstrate the effectiveness of policy changes in influencing practice patterns. The study findings highlight the potential opioid-sparing effects of ketamine as an analgesic and its potential role in decreasing overall rates of opioid use.

    Future research can evaluate relative rates of complications between ketamine and opioids, as well as their concurrent use and use as rescue therapy. These findings are unique to the US military and combat casualties as it relates to the implementation of TCCC guidelines. Ketamine usage patterns and potential opioid-sparing effects can be further evaluated in the civilian hospital and prehospital settings.

    Data availability statement

    Data may be obtained from a third party and are not publicly available. Data were obtained through a data sharing agreement (DSA) with the Joint Trauma System (JTS) through the Defense Health Agency and are only available to those listed on the DSA.

    Ethics statements

    Patient consent for publication

    Ethics approval

    The study was approved by the Navy Medicine Readiness and Training Command San Diego Institutional Review Board (NMCSD.2017.0049) and was part of a data sharing agreement with the Defense Health Agency (DHA).

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    Footnotes

    • Contributors SLW, AW and EL developed the hypothesis and research topic. SLW and AW obtained the data and crafted the data sharing agreement with the Defense Health Agency (DHA). SLW, AW and TCM developed the analysis questions. TCM analysed the data. All authors contributed to the creation of the manuscript. SLW is responsible for the overall work as the guarantor. SLW accepts full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.