Journal Club: Ketamine Versus Morphine for Pain Control

Author: Jacob Stelter, MD (EM Resident Physician, PGY-1, NUEM) // Edited by: Lora Alkhawam, MD (EM Resident Physician, PGY-4, NUEM) // Expert Reviewer: Danielle McCarthy, MD

Citation: [Peer-Reviewed, Web Publication] Stelter J, Alkhawam L (2016, February 16). Journal Club: Ketamine Versus Morphine For Pain Control. [NUEM Blog. Expert Peer Review by McCarthy DM]. Retrieved from


Ketamine has recently gained popularity amongst emergency physicians, and discussions about its efficacy and safety continue to shape practice in emergency medicine (EM).  Ketamine can be of use in multiple clinical applications and situations, however it is most commonly utilized in the emergency department (ED) for procedural sedation. Studies have also shown that ketamine has significant analgesic properties at sub-dissociative doses.  However, in order to promote ketamine from its current status of “novelty” to become “standard of care” in pain management, we must be convinced of its comparative effectiveness.  A study recently published in the Annals of Emergency Medicine compares ketamine’s analgesic properties to that of morphine, a narcotic pain medication. This article may be practice changing as it gives emergency physicians an alternative medication with which to treat pain among patients presenting to the emergency department.

The Study

Motov S, Rockoff B, et al. Intravenous sub-dissociative dose ketamine versus morphine for analgesia in the emergency department: A randomized controlled trial. Annals of Emergency Medicine. 2015;66(3):222-9.

Study Design

The study design was a prospective, randomized, double-blind controlled trial that had been approved through an Institutional Review Board.


The study was performed at Maimonides Medical Center in New York.  The patients selected were between the ages of 18 and 55 that had pain of the abdomen, back, flank or musculoskeletal system that they were rating at least a 5 out of 10 (on a scale from 0 to 10), and that necessitated narcotic pain medication per the attending.  Multiple exclusion criteria are listed in the article and included pregnancy or breast-feeding, AMS, obesity, unstable vitals, and history of head trauma as well as psychiatric illness or known chronic pain. 

Intervention Protocol

The intervention protocol started with patients rating their pain as at least a 5 out of 10 and an attending physician deeming that the patient could safely be treated with narcotic pain medication. The patients (90 total) that consented to be in the study were randomized to either the ketamine group or the morphine group.  The pharmacist then prepared either 0.3 mg/kg of ketamine or 0.1 mg/kg of morphine, provided the syringe containing the drug to the nurse in a blinded manner, and then the nurse delivered the drug via an IV to the patient. Hence, the nurses, providers, and patients were blinded to which medication was being delivered.

Outcome Measures

The primary outcome was reduction of the patients’ pain scores at 30 minutes after administration of the medication.  The secondary outcome analyzed was whether or not fentanyl was required for further pain control at either 30 or 60 minutes post-administration of the medication.  Changes to vital signs or noted adverse effects were also included in the analysis.


The mean age of participants were 35 in the ketamine group and 36 in the morphine group.  45 patients were enrolled into each arm of the study.  Demographics and starting vital signs were equal in both arms.  The average amount of ketamine given was 21.8 mg and the average amount of morphine given was 7.7 mg.  At the start, the baseline pain scores for ketamine and morphine were 8.6 and 8.5, with a reduction at 15 minutes to 3.2 and 4.2 and at 30 minutes to 4.1 and 3.9, respectively.  This is summarized in Table 2 from the original article.  



The reduction in pain between the two groups was not statistically significant.  However, the adverse reactions seen in both groups were significantly different for the first 15 minutes, with the ketamine group experiencing more adverse effects than the morphine group.  However, most of these side effects dissipated by 30 minutes, returning both groups to a low level of adverse effects that was about the same.  This can be seen in more detail in Table 3 from the original article.



These results are important and potentially practice changing.  This study demonstrates that ketamine has the same analgesic effect as morphine, effectively giving emergency physicians another medication option for use in treating acute pain in the ED.  This study has multiple strengths, which include the randomization process, which resulted in groups with similar baseline characteristics.  In addition, the study was double blinded such that the healthcare providers and patients did not know which medication was being given, further increasing the internal validity of this study.  The external validity of this study is a limitation, in that it was a single-center trial and only 90 patients were enrolled, which limits the study’s power and generalizability.  Another limitation is that chronic pain patients were excluded from this study.  However, this patient population could potentially benefit from ketamine for pain control. While more adverse effects were seen initially in the ketamine group, such as dizziness, disorientation, mood changes, and nausea, these were temporary, as most resolved by the 30 minute mark.  The clinical significance and impact on patient experience of these temporary side effects deserves further investigation before drawing conclusions regarding safety.

Future Studies

This study has opened the door to future studies, specifically larger, multi-center trials that could increase the generalizability of these findings and also, potentially using ketamine for pain control in chronic pain patients.

Take home points

  • Ketamine is just as effective as morphine in pain control for pain complaints commonly seen in the ED.
  • Ketamine has great potential to be used in multiple types of pain.
  • Ketamine is generally safe in the sub-dissociative dose of 0.3 mg/kg, with side effects being minor, including dizziness, nausea, and mood changes.  Most side effects resolved by 30 minutes.
  • This study is potentially practice-changing in that is shows that EM physicians have a safe alternative to IV narcotics in patients presenting with pain to the emergency department.

Expert Review

Hi Jacob, 

This is a nice review of the recent article by Motov and colleagues.  With “pain” being the most frequent complaint seen in the ED, it is rare that a shift will pass without needing to administer analgesics.  I believe that two separate phenomenon are responsible for emergency physicians (EP) taking a closer look at Ketamine as a sole agent for analgesia:  

  • There is increasing medical, policy, and media focus on the epidemic of prescription opioid related deaths that has prompted many emergency physicians to reflect on their own practice of using opioids.
  • There is an increasing body of data supporting the safety of Ketamine as an agent for procedural sedation which has resulted in a resurgence of the use Ketamine in the adult ED (both in combination (e.g.: “ketofol”) and as a sole agent). 

Thus, just as EPs are being prompted to rethink our use of opioids there is a growing familiarity with another agent that is useful for treating pain and has a wide therapeutic window.

So, the big question…is this practice changing?  Will I replace every dose of Morphine or Dilaudid with Ketamine in my daily practice?  Probably not….however, that does not mean that this study won’t influence my practice.  For patients that I consider good candidates for Ketamine as a single agent, this article informs the conversation. 

I believe that one of the biggest barriers to using Ketamine (or any non-opioid analgesic) is the culture of how we treat pain in the ED—both patients’ expectations and providers’ habits.  In order to have a cultural shift, two of the key ingredients are data and exposure.  We need data to support the proposed change and then all people involved (doctors, nurses, patients) need to be exposed to the change and realize that it is not a big, scary thing.  The Motov article is a step in the right direction of providing the data to drive the cultural shift because of the population chosen for the study.  The focus on the acute pain, rather than chronic pain patient, demonstrates that ketamine has more range and applicability than studies in other settings or with other patients. 

As you may know, a lot of my research is about doctor-patient communication. If I were having the conversation with a patient about why I was choosing ketamine to control their pain, the data in this article allows me to explain that this option is safe and effective “in patients like you.” One could explain that the medicine we want to give you works just as well as morphine at relieving pain and that although it has a slightly higher chance of side effects for the first 30 minutes, these side effects are minor.  You may ask: why do we even need to talk to patients about this? …we don’t regularly explain our rationale for a specific antibiotic to patients. Well, patient expectations surrounding pain, previous experience with opioids (“I think it started with a D…”), as well as a cultural awareness of opioid medication names all contribute to the need for this conversation, particularly in patients with chronic pain.  Additionally, nursing staff may be unfamiliar with Ketamine at sub-dissociative doses and associate it with the hassle of procedural sedation.  Reviewing this article with your nursing staff and educating them on the analgesic effectiveness and minor adverse effects may help to decrease resistance and slowly start a cultural shift.  

So, going back to the original question…is this practice changing?  This article supplies a piece of data that is needed to enable a shift in practice.  More data is needed in the ED setting to refine questions related to dosing, optimal patient population, and use as an adjunct versus sole agent.  However, incorporating this data into the current cultural trend towards opioid reduction, I believe we will begin to see a lot more Ketamine in the near future….So, will I replace every dose of Morphine or Dilaudid with Ketamine?  Not yet… 


Danielle McCarthy, MD

Assistant Professor; Department of Emergency Medicine, Northwestern University, Feinberg School of Medicine [Publications]


  • Motov S, Rockoff B, et al. Intravenous sub-dissociative dose ketamine versus morphine for analgesia in the emergency department: A randomized controlled trial. Annals of Emergency Medicine. 2015;66(3):222-9.
  • Miller JP et al. Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. Am J Emerg Med. 2015 Mar;33(3):402-8. 
Posted on February 16, 2016 and filed under Pain Management, EBM.