Skip to main content

The Opioids Issue: Morphine versus All Comers



by: Eric Widera (@ewidera)

Next year marks morphine's 200th anniversary as an analgesic (while it was discovered in 1804, it was first marketed to the public in 1817).  In honor of this historic event, I'm going to dedicate this GeriPal post to morphine by describing three recent trials that continue to show that morphine can hold its own when it comes to pain relief.

1. A randomized control trial of morphine vs either codeine and tramadol

We’ve never held back our disdain for the likes of codeine and tramadol on GeriPal, so why stop now? A great study recently came out that evaluated the use of “weak opioids” (you know, those step II drugs on the WHO  analgesic ladder) versus morphine for the relief of cancer related pain. This was a 28-day, open-label randomized controlled study done in 240 opioid na├»ve adults with moderate cancer pain (4-6 out of 10 pain). The participants were given either oral morphine or a weak opioid (tramadol with or without paracetamol or codeine in fixed combination with paracetamol.)  

The primary outcome of a pain reduction of 20% or more from baseline occurred in 88% of the low-dose morphine and in 58% of the weak-opioid group (odds risk, 6.18; 95% CI, 3.12 to 12.24; P,.001). The benefits of morphine over tramadol/codiene were evident as early as the 1 week observation point. Clinically meaningful (30%) and highly meaningful (50%) pain reduction from baseline was also significantly higher in the low-dose morphine group.  A change in the assigned treatment occurred more frequently in the tramadol/codiene group, because of inadequate analgesia. Adverse effects were similar in both groups.

This is just more evidence that morphine is a more effective mediation to reduce pain than tramadol and codeine. Combining this with other studies on the risks of tramadol, I’m not sure why one would ever chose these “weak opioids." I know I never do. It also calls into question the whole idea of a step II in the WHO analgesic ladder.

2. Another randomized control study of morphine or oxycodone for cancer-related pain

This is a little bit older of a study (dates back all the way to 2015) but a great one from my point of view. It was a randomized control study looking at the the clinical response to oral morphine vs. oral oxycodone when used as first-line or second-line (after switching) treatment in patients with cancer-related pain. In the first part of this study, patients were randomized to either of these agents and the doses were titrated until the patient reported adequate pain control. If they didn't respond to the first-line opioid (either because of inadequate analgesia or unacceptable adverse effects) they were switched to the other opioid.

They found no significant difference between the numbers of patients responding to morphine (62%) or oxycodone (67%) when used as a first-line opioid, or when used as a second line therapy when switching due to inadequate response to the first line therapy. Of most interest, over half of those who didn't respond to first line therapies got relief with the second line therapy, giving some much needed evidence to back up the practice of opioid rotations.

3. Morphine versus NSAIDs for malignant pleural effusion pleurodesis

What’s better, opioids or NSAIDs for pain control in patients with malignant pleural effusions? This non-blinded study looked at that question among 320 patients requiring pleurodesis in 16 UK hospitals from 2007 to 2013 (they also looked at the effects of different sizes of chest tubes, but I wont talk about that here). Patients with malignant effusions were all given acetaminophen around the clock and randomized to receive either oral morphine (starting at 10mg QID to max of 80mg/24 hours) vs ibuprofen (starting at 800mg TID to max of 2.4g/24 hours). In either group, if pain got to bad, patients could use IV morphine as a breakthrough.

The authors of the study found that mean pain scores as measured by a 100 point visual analog scale were no different in the morphine PO group vs the NSAID group (mean VAS score, 23.8mm in opioid vs 22.1 mm in NSAID; adjusted difference, −1.5 mm; P = .40). However, the NSAID group required more rescue analgesia (38% in NSAID group and 26% in oral morphine). Adverse effects looked similar although the NSAID group had a statistically significant increase in creatinine that was clinically less significant (by 0.1 mg/dl).

What am I taking from this study? Well, to put bluntly, there is little evidence that NSAIDs are better than opioids for for malignant pleural effusion pleurodesis, and even when you used them, a third of patients will still required morphine for breakthrough pain control.

Comments

Mike Steinman said…
Eric, in the second study you cite, to what extent is there evidence that opioid rotation provided true benefit, as opposed to - dare I say it - regression to the mean in terms of pain control.
That graphic though! Body blow! Body blow! Uppercut!
This comment has been removed by the author.
Eric Widera said…
To the individual who dared to mention the term "regression to the mean" - you won this round. It would of been nice to have a group of non-responders who didn't switch to a new opioid to see what happened to their pain levels.

Finally someone commented on the graphic. Thats Sinclair. That was my favorite part of the post!

Popular posts from this blog

The Future of Palliative Care: A Podcast with Diane Meier

There are few names more closely associated with palliative care than Diane Meier.  She is an international leader of palliative care, a MacArthur "genius" awardee, and amongst many other leadership roles, the CEO of the Center to Advance Palliative Care (CAPC).  We were lucky enough to snag Diane for our podcast to talk about everything we always wanted to ask her, including:
What keeps her up at night?Does palliative care need a national strategy and if so why and what would it look like?The history of CAPC and the leadership centersAdvice that she has for graduating fellows who want to continue to move palliative care forward as they start their new careersWhat she imagines palliative care will look like in 10 or 15 years?What is the biggest threat facing palliative care? So take a listen and if you want to dive a little deeper, here are two articles that we discussed during the podcast:
A National Strategy For Palliative Care. Health Affairs 2017Palliative Care Leadership…

Advance Care Planning before Major Surgery: A Podcast with Vicky Tang

This week's podcast is all about the intersection of geriatrics, palliative care, advanced care planning and surgery with our guest Dr. Vicky Tang.  Vicky is an assistant professor and researcher here at UCSF.  We talk about her local and national efforts focused on this intersection, including:
Her JAMA Surgery article that showed 3 out of 4 older adults undergoing high risk surgery had no advance care planning (ACP) documentation. Prehab clinics and how ACP fits into these clinicsThe Geriatric Surgery Verification Quality Improvement Program whose goal is to set the standards for geriatric surgical care including ACP discussions prior to surgeryHow frailty fits in and how to assess it (including this paper from JAGS on the value of the chair raise test) So take a listen and check out some of those links.  For those who want to take a deeper dive into how GeriPal and surgery fit together, check out these other podcasts: Zara Cooper on Trauma Surgery, Geriatrics, and Palliative Car…

The Dangers of Fleet Enemas

The dangers of oral sodium phosphate preparations are fairly well known in the medical community. In 2006 the FDA issued it’s first warning that patients taking oral sodium phosphate preparations are at risk for potential for acute kidney injury. Two years later, over-the-counter preparations of these drugs were voluntarily withdrawn by the manufacturers.  Those agents still available by prescription were given black box warnings mainly due to acute phosphate nephropathy that can result in renal failure, especially in older adults. Despite all this talk of oral preparations, little was mentioned about a sodium phosphate preparation that is still available over-the-counter – the Fleet enema.

Why Oral Sodium Phosphate Preparations Are Dangerous 

Before we go into the risks of Fleet enemas, lets spend just a couple sentences on why oral sodium phosphate preparations carry significant risks. First, oral sodium phosphate preparations can cause significant fluid shifts within the colon …