Comparison of paravertebral anaesthesia to general anaesthesia for breast cancer surgery

What is the issue?

Breast cancer is one of the most common cancers in women. Surgical removal of the tumour is the main treatment; however, dissemination of cancer cells may occur due to tumour handling during surgery. The body's response to surgery (stress response or release of hormones and mediators) as well as drugs used to produce general anaesthesia (complete loss of consciousness), such as opioids and inhalational anaesthetics, can also depress immunity and promote cancer cell survival.

Paravertebral anaesthesia acts by numbing the nerves on one side of the body and can allow surgery to be performed without general anaesthesia. The lightly sedated participant can report pain, cold, thirst, or hunger during or after surgery, allowing timely treatment. This, combined with pain relief produced by paravertebral anaesthesia, has the potential to improve immunity, reduce surgical stress, and improve quality of life and cancer-free survival.

Review question

We collected and analysed data from all relevant studies to ascertain whether paravertebral anaesthesia would provide better quality of recovery and pain relief at rest and on movement, and to determine whether paravertebral anaesthesia would have any affect on mortality, compared to general anaesthesia.

Study characteristics

We included randomised controlled trials in which participants in one group received paravertebral anaesthesia with or without sedation and participants in the other group received general anaesthesia during breast cancer surgery. We did not include studies in which paravertebral anaesthesia was administered in addition to general anaesthesia and then this was compared to the use of general anaesthesia.

Key results

Nine studies involving 614 participants were included. Four studies were conducted in Europe, three in Asia, and one each in Africa and North America. All studies took place in medical college hospitals with no external funding.

When reviewing evidence on the quality of recovery, these studies reported various outcomes. It was found that paravertebral anaesthesia:

• may reduce 24-hour postoperative analgesic use (61 per 1000 versus 480 per 1000 in the general anaesthesia group);

• probably reduces the incidence of postoperative nausea and vomiting (72 per 1000 versus 340 per 1000 in the general anaesthesia group);

• probably reduces pain at 2 hours (by 2.95 points on a 0 to 10 point scale) and may reduce pain at 24 hours at rest (0.21 points on a 0 to 10 point scale) compared to general anaesthesia; and

• may reduce pain on movement at 6 hours and at 24 hours post surgery (at 6 hours by 2.57 points; at 24 hours by 2.12 points on a scale of 0 to 10) compared to general anaesthesia.

No study reported on death with each anaesthetic technique. None of the included studies reported on disease-free survival, chronic pain, or quality of life after breast cancer surgery, probably because these outcomes were not envisaged or planned.

Reports of adverse events with paravertebral block were rare. Out of 290 participants who received paravertebral anaesthesia, two developed epidural spread, four had minor bleeding, and one had pleural puncture. Seventeen of 240 participants developed Horner's syndrome. All adverse events were self-limited and resolved without treatment.

Quality of the evidence

Most evidence was judged to be of moderate certainty, meaning that we are moderately confident in the reported result. In some cases, evidence was seen to be of low certainty, meaning that our confidence in the reported result is limited.

Authors' conclusions: 

Moderate-certainty evidence shows that paravertebral anaesthesia probably reduces PONV, hospital stay, postoperative pain (at 2 hours), and time to ambulation and results in greater patient satisfaction on the first postoperative day compared to general anaesthesia. Paravertebral anaesthesia may also reduce postoperative analgesic use and postoperative pain at 6 and 24 hours at rest and on movement based on low-certainty evidence. However, RCTs using validated questionnaires are needed to confirm these results. Adverse events observed with paravertebral anaesthesia are rare.

Read the full abstract...
Background: 

Breast cancer is one of the most common cancers among women. Surgical removal of the cancer is the mainstay of treatment; however, tumour handling during surgery can cause microscopic dissemination of tumour cells and disease recurrence. The body's hormonal response to surgery (stress response) and general anaesthesia may suppress immunity, promoting tumour dissemination. Paravertebral anaesthesia numbs the site of surgery, provides good analgesia, and blunts the stress response, minimising the need for general anaesthesia.

Objectives: 

To assess the effects of paravertebral anaesthesia with or without sedation compared to general anaesthesia in women undergoing breast cancer surgery, with important outcomes of quality of recovery, postoperative pain at rest, and mortality.

Search strategy: 

On 6 April 2020, we searched the Specialised Register of the Cochrane Breast Cancer Group (CBCG); CENTRAL (latest issue), in the Cochrane Library; MEDLINE (via OvidSP); Embase (via OvidSP); the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal; and ClinicalTrials.gov for all prospectively registered and ongoing trials.

Selection criteria: 

We included randomised controlled trials (RCTs) conducted in adult women undergoing breast cancer surgery in which paravertebral anaesthesia with or without sedation was compared to general anaesthesia. We did not include studies in which paravertebral anaesthesia was given as an adjunct to general anaesthesia and then this was compared to use of general anaesthesia.

Data collection and analysis: 

Two review authors independently extracted details of trial methods and outcome data from eligible trials. When data could be pooled, analyses were performed on an intention-to-treat basis, and the random-effects model was used if there was heterogeneity. When data could not be pooled, the synthesis without meta-analysis (SWiM) approach was applied. The GRADE approach was used to assess the certainty of evidence for each outcome.

Main results: 

Nine studies (614 participants) were included in the review. All were RCTs of parallel design, wherein female patients aged > 18 years underwent breast cancer surgery under paravertebral anaesthesia or general anaesthesia.

None of the studies assessed quality of recovery in the first three postoperative days using a validated questionnaire; most assessed factors affecting quality of recovery such as postoperative analgesic use, postoperative nausea and vomiting (PONV), hospital stay, ambulation, and patient satisfaction.

Paravertebral anaesthesia may reduce the 24-hour postoperative analgesic requirement (odds ratio (OR) 0.07, 95% confidence interval (CI) 0.01 to 0.34; 5 studies, 305 participants; low-certainty evidence) compared to general anaesthesia. Heterogeneity (I² = 70%) was attributed to the fixed dose of opioids and non-steroidal analgesics administered postoperatively in one study (70 participants), masking a difference in analgesic requirements between groups.

Paravertebral anaesthesia probably reduces the incidence of PONV (OR 0.16, 95% CI 0.08 to 0.30; 6 studies, 324 participants; moderate-certainty evidence), probably results in a shorter hospital stay (mean difference (MD) -79.39 minutes, 95% CI -107.38 to -51.40; 3 studies, 174 participants; moderate-certainty evidence), and probably reduces time to ambulation compared to general anaesthesia (SWiM analysis): percentages indicate vote counting based on direction of effect (100%, 95% CI 51.01% to 100%; P = 0.125; 4 studies, 375 participants; moderate-certainty evidence).

Paravertebral anaesthesia probably results in higher patient satisfaction (MD 5.52 points, 95% CI 1.30 to 9.75; 3 studies, 129 participants; moderate-certainty evidence) on a 0 to 100 scale 24 hours postoperatively compared to general anaesthesia.

Postoperative pain at rest and on movement was assessed at 2, 6, and 24 postoperative hours on a 0 to 10 visual analogue scale (VAS). Four studies (224 participants) found that paravertebral anaesthesia as compared to general anaesthesia probably reduced pain at 2 postoperative hours (MD -2.95, 95% CI -3.37 to -2.54; moderate-certainty evidence). Five studies (324 participants) found that paravertebral anaesthesia may reduce pain at rest at 6 hours postoperatively (MD -1.54, 95% CI -3.20 to 0.11; low-certainty evidence). Five studies (278 participants) found that paravertebral anaesthesia may reduce pain at rest at 24 hours postoperatively (MD -1.19, 95% CI -2.27 to -0.10; low-certainty evidence). Differences in the methods of two studies (119 participants) and addition of clonidine to the local anaesthetic in two studies (109 participants), respectively, contributed to the heterogeneity (I² = 96%) observed for these two outcomes.

Two studies (130 participants) found that paravertebral anaesthesia may reduce pain on movement at 6 hours (MD-2.57, 95% CI -3.97 to -1.17) and at 24 hours (MD -2.12, 95% CI -4.80 to 0.55; low-certainty evidence). Heterogeneity (I² = 96%) was observed for both outcomes and could be due to methodological differences between studies.

None of the studies reported mortality related to the anaesthetic technique. Eight studies (574 participants) evaluated adverse outcomes with paravertebral anaesthesia: epidural spread (0.7%), minor bleeding (1.4%), pleural puncture not associated with pneumothorax (0.3%), and Horner's syndrome (7.1%). These complications were self-limiting and resolved without treatment.

No data are available on disease-free survival, chronic pain, and quality of life.

Blinding of personnel or participants was not possible in any study, as a regional anaesthetic technique was compared to general anaesthesia. Risk of bias was judged to be serious, as seven studies had concerns of selection bias and three of detection bias.

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