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Opioid-sparing anaesthesia and analgesia

Could reducing or even avoiding the use of opioids around the time of surgery have a role to play in opioid stewardship? Dr John Wittle explains.
Intravenous medications administered by slow infusion
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Could reducing or even avoiding the use of opioids during general anaesthesia and in the early postoperative period have a role to play in promoting opioid stewardship?

In this step, Dr John Whittle, Consultant in Anaesthesia at UCLH and Associate Professor in Perioperative Medicine at UCL, and Drs Sandra Maurício and Shalini Patel, Perioperative Medicine Fellows at UCLH, help us find out.

Why do we use opioids at all during general anaesthesia? Isn’t the patient asleep?

Before the introduction of opioids to routine anaesthetic practice, the main objectives of general anaesthesia – unconsciousness, immobility, and the control of the autonomic response to surgical stimulation – were achieved with high doses of hypnotic agents.

During general anaesthesia the patient does not experience pain, as this is a subjective experience which requires consciousness. There is still activation of nociceptive pathways which cause increased sympathetic activity via the nociceptive-medullary-autonomic circuit [1].

Mu-receptor agonism by opioids along these pathways reduces nociceptive signals and consequently sympathetic output.

Very large doses of hypnotic agents are required if they are going to be used in isolation to blunt this autonomic response, leading to severe cardiovascular instability and delayed emergence from anaesthesia.

The use of opioids during general anaesthesia therefore became a widely accepted way of controlling the increases in blood pressure and heart rate caused by surgical stimulus, in what came to be known as ‘balanced anaesthesia’.

High opioid doses are also used in patients with reduced myocardial function, as they cause little myocardial depression and the diminished autonomic stimulation provides haemodynamic stability [2].

What are the benefits of opioid-sparing and opioid-free anaesthesia?

Reducing or avoiding intraoperative opioid administration is likely to reduce dose-related early postoperative opioid-related adverse drug events (ORADEs), such as those we discussed in Step 2.13: nausea and vomiting, reduced intestinal transit, sedation and opioid-induced ventilatory impairment (OIVI) [1]. This is particularly appealing in those patient groups most at risk of these adverse effects such as the obese, those with respiratory disease, and patients undergoing abdominal surgery.

Avoiding intraoperative and early postoperative opioid use also has the potential of reducing the incidence of opioid-induced hyperalgesia, a phenomenon which is dose-related and which is also known to occur acutely [3], although its clinical relevance in this setting has not been established.

The use of opioid-free and opioid-sparing techniques is also likely to be of particular use in patients who are very opioid tolerant, or who are on buprenorphine-based opioid substitution therapy, in whom very large doses of opioids would otherwise be required (see Step 3.18).

There is also some preclinical evidence and uncontrolled clinical studies which suggest that opioids may represent a risk factor in cancer recurrence when used in cancer surgery, although a recent review [4], as well as a large randomised controlled trial, concluded there was insufficient evidence to support this association [5-6].

How are opioid-free anaesthesia and analgesia achieved?

Opioid-free anaesthesia is achieved through maximising the use of local and regional anaesthetic techniques as well as using a multimodal anti-nociceptive approach to block inflammatory, nociceptive and sympathetic pathways.

Opioid-free analgesia uses the same analgesic and adjuvant drugs, but extends them, with different regimens, into the postoperative period.

The table below summarises the intravenous analgesics and adjuvants that are frequently used in opioid-free anaesthesia and analgesia, namely alpha-2 adrenoreceptor agonists, N-methyl-D-aspartate (NMDA)-receptor antagonists, intravenous local anaesthetics, steroidal and non-steroidal anti-inflammatory drugs. Several combinations and doses can be used, and specific protocols vary. A screen-readable version can be found in the Downloads section at the end of this step.

Intravenous drugs used in opioid-free anaesthesia and analgesia, including mechanisms, specific properties, benefits and adverse effects

Table showing intravenous drugs used in opioid-free anaesthesia and analgesia, including mechanisms, specific properties, benefits and adverse effects

What are the potential drawbacks of opioid-free anaesthesia and analgesia?

The analgesics and adjuncts used in opioid-free anaesthesia and analgesia have their own adverse event profile and contraindications.

Alpha-2 agonists can cause hypotension and sedation, ketamine can cause psychotropic side-effects, and beta-blockers can cause hypotension and increase the risk of stroke.

Many of the agents used cannot be titrated to individual requirements or have a maximum daily dose, such as NSAIDs and paracetamol. Additionally, agents such as ketamine or lidocaine, when used in the postoperative phase, require high-dependency monitoring and entail intravenous infusions which can hinder ambulation and therefore delay recovery.

Of note, gabapentinoids, which had previously been commonly recommended in a number of enhanced recovery pathways as opioid-sparing agents, are no longer routinely recommended in this setting. Their use is associated with a statistically but not clinically significant reduction in postoperative pain and opioid consumption, and it is associated with an increased risk of serious adverse events including OIVI when co-administered with opioids [7].

How effective are opioid-free anaesthesia and analgesia in promoting opioid stewardship?

There is evidence that the use of opioid-free anaesthesia and analgesia reduces the incidence of postoperative nausea, vomiting and sedation, as well as providing improved pain experience (especially with regional analgesia) and reduced opioid use in the early postoperative period [6].

There is so far no evidence that opioid-free anaesthesia and analgesia prevent persistent postoperative opioid use (PPOU), alter prescribing at discharge or the risk of diversion and misuse, even with the concurrent use of regional anaesthesia. [1-2, 7]

There is also little evidence that opioid-free anaesthesia and analgesia provide benefits above and beyond those of opioid-sparing anaesthesia and analgesia.

Although there are many potential advantages to opioid-free analgesia, it is not clear whether it is practically possible during the whole postoperative period, and many studies which purport to look at opioid-free analgesia provide opioids as rescue or at some point in the postoperative phase. There is also a lack of studies looking at the efficacy of opioid-free analgesia after discharge [8].

Your turn now

Use the comments section below to share your thoughts and experiences.
What do you think about the role of opioid-free anaesthesia and analgesia? In your view, what is the potential role for these practices? Why do you think there is little evidence suggesting an effect on postoperative prescribing from the use of opioid-free anaesthesia and analgesia?

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1. Egan TD. Are opioids indispensable for general anaesthesia? Br J Anaesth 2019;122:e127-35.

2. Alexander JC, Patel B, Joshi GP. Perioperative use of opioids: Current controversies and concerns. Best Pract Res Clin Anaesthesiol 2019;33:341-51.

3. Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth 2014;112:991-1004.

4. Wall T, Sherwin A, Ma D, et al. Influence of perioperative anaesthetic and analgesic interventions on oncological outcomes: a narrative review. Br J Anaesth 2019;123:135-50.

5. Sessler DI, Pei L, Huang Y, et al. Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial. Lancet 2019;394:1807-15.

6. Kumar K, Kirksey MA, Doung S, Wu CL. A Review of Opioid-Sparing Modalities in Perioperative Pain Management: Methods to Decrease Opioid Use Postoperatively. Anesth Analg 2017;125:1749-1760.

7. Macintyre PE, Quinlan J, Levy N, et al. Current Issues in the Use of Opioids for the Management of Postoperative Pain: A Review. JAMA Surg 2022;157:158-66.

8. Shanthanna H, Ladha KS, Kehlet H, Joshi GP. Perioperative Opioid Administration. Anesthesiology 2020;134:645–59.

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