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New Study: Ketamine Can Bring Down Use of Opioids

Written by Sarah Friedman

Opioid use is out of control in the US, and for many addicts, the whole awful ride started with a legitimate pain issue. So, what to do when it’s your treatment that causes your problem? Maybe, find a better treatment. A new study backs up that ketamine during surgery can lessen the need for opioids to manage pain after. Read on to find out more about this, and why ketamine should immediately replace the drug which is killing close to 100,000 people a year.

The study

This was not a study that involved finding test subjects and having them participate in clinical trials. This study, like many put out today, was done by reviewing previous research to find connections. This method of research must be taken with a grain of salt, as there are no controls, and the study writers have nothing to do with data collection. Even so, though these studies are often thrown together in what seems like a haphazard manner for the purpose of gaining headlines, (often off of misguided, misquoted or misused research), they often do provide some insight, like the study I’m talking about now.

The study, entitled A Systematic Review of the Efficacy and Safety of Ketamine in Total Joint Arthroplasty evaluated data from studies found via the databases: MEDLINE, Embase and Cochrane Central Register of Controlled Trials. The intended purpose was to evaluate how safe and useful ketamine is in primary hip and knee replacement cases; in order to support the combined clinical practice guidelines of different medical associations.

Studies included were published before 2020, and on the subject of total joint arthroplasty treatment. According to the study, “All included studies underwent qualitative assessment and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of ketamine. After a critical appraisal of 136 publications, 7 high-quality studies were included for analyses.” In total, four studies showed intraoperative ketamine as superior to placebo for pain relief after surgery, while three studies didn’t find a significant difference compared to placebo.

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Six studies were analyzed for postoperative opioid use, and of them, five came to the conclusion that intraoperative ketamine allowed for less overall opioid intake after the operation, though the last one did not find a significant difference in comparison to placebo. Four studies also looked at complications, and in those studies it was found that versus a placebo, ketamine brought down the instances of postoperative nausea and vomiting.

In the write-up, researchers state: “Intraoperative intravenous ketamine reduces postoperative opioid consumption and may reduce postoperative pain and nausea and vomiting after primary TJA… Ketamine administered intraoperatively is safe but may increase the risk of postoperative delirium and hallucinations, particularly among elderly patients after TJA.”

Implications of the study

The term ‘intraoperative ketamine’ refers to ketamine used during an operation, not before or after. So its not a study looking at pain management of ketamine versus anything else. Rather, it looks at the outcome of using ketamine vs other medications during an operation. The term ‘arthroplasty’ refers to the replacement of a joint, like hips or knees.

In this process, an artificial joint is put in place of a damaged joint. Though sometime just one part is replaced, it’s very often the entire joint. All studies in this evaluation were done on participants with total joint replacements. Total hip arthroplasty is referred to as THA, total knee arthroplasty is referred to as TKA, and total joint arthroplasty is referred to as TJA.

One of the implications of the study, is that the use of ketamine during an operation, can have a lasting benefit after the operation. Enough so that less opioid medication is then needed to manage pain. This implies that effects of the ketamine go on for a significant period of time.

After all, a medication that simply wears off, requires something new to be taken to counter pain. Think of how much pain is involved with having your hip or knee torn out, and a fake one put in. That’s exactly what’s happening, and it would be extremely difficult to get rid of postoperative pain considering the magnitude of the operation.

However, if the ketamine used during the operation, can create a benefit wherein patients don’t require postoperative opioids – (or less of them), this speaks volumes to the ability of ketamine to bring down the opioid problem. Keep in mind, if its shown to bring down post-operative opioid use for joint replacements, chances are that this is the case for other surgeries as well. And the implication to that is huge, especially in a country (and world) with an increasing problem with opioid deaths.

How big is the problem with opioids? Preliminary overdose numbers for 2021 put deaths at over 107,000 according to the CDC, for the US alone. No number was given for synthetic opioid overdoses specifically, but we can know that the number is high, and takes up the majority of the deaths. We know that because this is a trajectory we’ve been looking at for a while. In 2020, overdose deaths totaled over 93,000, with over 68,000 attributed to opioids. In 2019, the overdose total was approximately 73,000, with around 48,000 earmarked as opioid deaths.

Can ketamine bring down opioid use for pain?

If you’re on opioids because you like how they make you feel; it probably doesn’t matter to you how they affect pain. If you’re on them because you had a pain issue that since resolved, but led to an addiction in the process; it also probably won’t matter to you if ketamine is a better option for pain relief. But if you’re taking opioids to deal with a pain issue now, and that pain issue keeps you on the meds; then this information is much more relevant.

There are two interesting aspects of ketamine. The first is that it treats both acute and chronic pain, but without lowering breathing and blood pressure rates. Opioids depress the central nervous system, and overdose occurs when the body can no longer handle the downer effect; which is an issue because of tolerance to other effects. As ketamine can treat pain without the same kind of depression to the CNS, its not associated with overdose deaths. To the point that there really is no death toll. This isn’t to say no one was ever hurt with ketamine, but the numbers are so negligible, they’re nearly impossible to find.

The other interesting thing about ketamine for pain, is that it lasts well after the treatment. And I don’t mean for 4-6 hours. According to research, it can last for weeks at a time, possibly even months. This is similar to the same thing seen with ketamine treatments for depression and other psychological issues. After however many initial sessions it takes, the effects can last weeks to months for those who do respond. Can opioids do that? Not a chance. One of the big issues with opioid addiction, came from the initial lies around Oxycontin lasting a particular amount of time, which it actually rarely did.

If all of this sounds like not what you’re used to hearing, check out the research yourself. Like this 2020 review Ketamine vs Opioids for Acute Pain in the Emergency Department, or this 2018 review, A Systematic Review and Meta-analysis of Ketamine as an Alternative to Opioids for Acute Pain in the Emergency Department, or this 2019 research entitled Effect of Intranasal Ketamine vs Fentanyl on Pain Reduction for Extremity Injuries in Children: The PRIME Randomized Clinical Trial. All of these show how ketamine gives opioids a run for their money when it comes to treating acute pain.

In terms of chronic pain, this review Ketamine for chronic pain: risks and benefits, from 2014 shows that after initial infusions, effects can last for up to three months. And this review from 2019 backs up the idea that pain relief is continuing after infusions, though it found a shorter period of up to about eight weeks max. In both these reviews for use with chronic pain, ketamine showed an ability on par, or better, than opioids for actual pain relief; with the benefit of continued effects well after treatment. And all this without the threat of addiction or death.

This new study backs up, in a roundabout way, that ketamine has a long-lasting effect. It strongly implies that ketamine used during a surgery, can influence the need for pain medication after surgery. To the point of lessening the need for opioid medications in postoperative care. Perhaps in the coming months to years, we’ll hear way more about this, and how ketamine in general, can replace the use of synthetic opioids for pain control.


The opioid situation is insanely awful, especially when considering it doesn’t have to happen. What all this research shows, more than anything, is that we’re continuously told the wrong story. And in continuously telling it wrong; more people die.

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About the author

Sarah Friedman

I look stuff up and and write stuff down, in order to make sense of the world around. And I travel a lot too.