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Summary

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgement
  7. Competing interests
  8. References

Eighteen published trials have examined the use of neuraxial magnesium as a peri-operative adjunctive analgesic since 2002, with encouraging results. However, concurrent animal studies have reported clinical and histological evidence of neurological complications with similar weight-adjusted doses. The objectives of this quantitative systematic review were to assess both the analgesic efficacy and the safety of neuraxial magnesium. Eighteen trials comparing magnesium with placebo were identified. The time to first analgesic request increased by 11.1% after intrathecal magnesium administration (mean difference: 39.6 min; 95% CI 16.3–63.0 min; p = 0.0009), and by 72.2% after epidural administration (mean difference: 109.5 min; 95% CI 19.6–199.3 min; p = 0.02) with doses of between 50 and 100 mg. Four trials monitored for neurological complications: of the 140 patients included, only a 4-day persistent headache was recorded. Despite promising peri-operative analgesic effect, the risk of neurological complications resulting from neuraxial magnesium has not yet been adequately defined.

Magnesium has analgesic properties, primarily related to the regulation of calcium influx into cells [1] and antagonism of N-methyl-d-aspartate (NMDA) receptors in the central nervous system [2, 3]. This analgesic effect was first demonstrated in humans in 1996 when magnesium was administered intravenously in the peri-operative period [4]. Since then, a number of additional trials investigating the analgesic efficacy of peri-operative intravenous magnesium have been published, with conflicting results [5–7]. One possible explanation for the reported variability in analgesic efficacy of magnesium administered intravenously may be limited passage of this molecule across the blood-brain barrier, which has been demonstrated even in the presence of induced systemic hypermagnesaemia [8–10]. Consequently, it has been suggested that an intrathecal injection would allow more effective magnesium activity at spinal cord NMDA receptors. Indeed, rat models reveal that direct intrathecal administration of magnesium enhances the antinociceptive effect of opioids for acute incisional pain [11], and suppresses nociceptive responses in neuropathic pain models [12]. The earliest clinical trials investigating intrathecal and epidural magnesium reported an increase in the median duration of analgesia [13] and decrease in opioid consumption by 25% [14], respectively.

However, neuraxial administration of magnesium is not without risk. Animal studies have reported histological neurotoxicity with weight-adjusted doses similar to those used in most human clinical trials to date [15], whereas two case reports have described patients suffering from disorientation [16] and continuous peri-umbilical burning pain [17] following the injection of magnesium into the neuraxis. Therefore, the dual objectives of this quantitative systematic review of the literature were to assess both the analgesic efficacy and the safety of neuraxial magnesium in the management of acute postoperative pain, to define better its role in modern clinical practice.

Methods

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgement
  7. Competing interests
  8. References

The methods of this review followed the recommendations of the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ (PRISMA) statement [18]. The authors searched the electronic databases MEDLINE (until January 2012), EMBASE (until January 2012), and the Cochrane Central Register of Controlled Clinical Trials (until January 2012) using the following population search terms: magnesium OR magnesium compounds. These search results were combined using the Boolean operator AND with the terms peri-operative care OR peri-operative period and focused by combination using AND with the terms analgesia OR analgesics OR pain OR pain management OR pain measurement OR pain threshold. The following words were also searched as keywords: magnesium*, periop*, peri-op*, perop*, intraop*, intra-op*, postop*, post-op*, analg*, and pain*. Finally, reference lists from the resulting publications were manually searched for any relevant trials not identified by the above search strategy. The resulting list of publications was limited to include only randomised controlled trials, English, French and German language publications, human and adult studies and the use of magnesium sulphate in the investigation arm. Only those trials comparing the administration of intrathecal or epidural magnesium to placebo were included in the present review.

The quality of the method used in each trial included was assessed using the Jadad criteria [19] on a scale from 1 (minimum) to 5 (maximum). Two authors (EA, SA) independently extracted the data and reviewed and scored each trial using this method with differences in extracted data or scoring resolved by discussion with a third author (RB). The trial characteristics recorded included: type of surgery; type of surgical anaesthesia; route of administration; dose of administered magnesium; and type of postoperative analgesia.

Specific outcomes sought from each publication were based on the American Society of Regional Anesthesia and Pain Medicine’s Acute Postoperative Pain Database initiative [20]. These included the acute pain-related endpoints: (i) onset time of sensory blockade; (ii) regression time of sensory blockade; (iii) onset time of motor blockade; (iv) regression time of motor blockade; (v) time to first analgesic request after neuraxial blockade; (vi) intravenous morphine consumption at 24 h postoperatively; (vii) pain scores at rest and on movement measured at 24 h postoperatively; (viii) early postoperative (0–6 h) intravenous morphine consumption; (ix) early postoperative (0–6 h) pain scores at rest and on movement; and incidences of (x) postoperative nausea and vomiting and (xi) pruritus within the first 24 h postoperatively. If not otherwise stated, it was assumed that reported pain scores had been assessed at rest.

The safety-related endpoints sought included: (i) temporary and permanent neurological complications defined based on terminology described in the American Anesthesiologists’ Society Closed Claims database project [21]; as well as (ii) hypotension; (iii) bradycardia; and (iv) sedation.

Mean and SD values, for analysed endpoints, were extracted from the text, tables or figures of each source publication. The authors of trials that failed to report the sample size or results as a mean and SD or SEM were contacted to request the missing data. All opioid use was converted to equianalgesic doses of intravenous morphine [22–24]. Similarly, pain scores reported as verbal rating or numeric rating scales were converted to a standardised 0–100 analogue scale to permit quantitative evaluation.

Each endpoint was analysed according to the route of magnesium administration (intrathecal, epidural, or intrathecal and epidural) and a meta-analysis was conducted if two or more trials reported the endpoint of interest. Meta-analyses were performed with the assistance of RevMan (version 5.1.6; Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration, 2011). This software estimates the weighted mean differences for continuous or categorical data, allowing comparison between groups with an overall estimate of the pooled effect. As most data were heterogeneous, analyses were performed using a random effects model and results are presented as mean difference or relative risk (RR) with 95% CI. I2 was determined to evaluate heterogeneity using thresholds for low (25%–49%), moderate (50–74%), and high (> 75%) levels [25]. Finally, the possibility of publication bias was assessed by calculating a funnel plot of standard error of the mean difference (y-axis) as a function of the mean difference (x-axis). A two-sided p-value < 0.05 was considered significant.

Results

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgement
  7. Competing interests
  8. References

Eighteen trials, including a total of 1145 patients, were included in the analysis (Fig. 1). Twelve publications were identified from the literature search strategy and six from scanning bibliographies.

image

Figure 1.  PRISMA flow diagram showing literature search results. Eighteen randomised controlled trials (RCTs) were ultimately used for the analysis.

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Trial characteristics are presented in Table 1. Sixty-seven per cent of the publications achieved a Jadad score of 4 or 5. Most trials were conducted on patients undergoing orthopaedic and lower limb surgery (8/18; 44.5%) [14, 26–32] or gynaecology and obstetric procedures (8/18; 44.5%) [13, 33–39]. The two remaining trials were conducted on patients undergoing major abdominal surgery [40] and thoracotomy [41]. Attempts were made to contact eight authors because of incomplete data [13, 14, 28, 30, 31, 36, 38, 41], but none provided the information requested.

Table 1. Trial characteristics.
ReferenceJadad scoreNumber of patients in magnesium group/placebo groupSurgerySexAnaesthesia strategyNeuraxial drugs other than magnesiumBolus dose of magnesiumEpidural infusion of magnesiumTotal dose in 24 hPostoperative analgesiaMethod of data extractionComment
  1. IV, intravenous; PCA, patient-controlled analgesia; PCEA, patient-controlled epidural analgesia

Intrathecal administration of magnesium
 [26]523/30Total hip and total knee arthroplastyBothSpinal anaesthesiaIntrathecal 15 mg levobupivacaine + 8 μg sufentanil94.5 mgNo50 mgIV PCA morphineGraphsFour groups included: control; intrathecal; intrathecal + epidural; and epidural. Data from the control and intrathecal groups were extracted
 [13]525/25Labour analgesiaFemaleSpinal anaesthesia + epidural analgesiaIntrathecal 25 μg fentanyl50 mgNo50 mgEpidural infusion of fentanyl + bupivacaine + adrenalineText
 [27]330/30Knee arthroscopyBothSpinal anaesthesiaIntrathecal 6 mg hyperbaric bupivacaine + 10 μg fentanyl50 mgNo50 mgIV + oral tramadolText/tables
 [34]534/31Caesarean deliveryFemaleSpinal anaesthesiaIntrathecal 10 mg isobaric bupivacaine + 10 μg fentanyl + 100 μ morphine100 mgNo100 mgIV paracetamolGraphs
 [29]540/39Lower extremity surgeryBothSpinal anaesthesiaIntrathecal 15 mg isobaric bupivacaine100 mgNo100 mgIV + oral tramadolTables
 [36]530/30Caesarean deliveryFemaleSpinal anaesthesiaIntrathecal 10 mg hyperbaric bupivacaine + 25 μg fentanyl50 mgNo50 mgIntramuscular diclofenacText/tables
 [41]529/29Posterolateral thoracotomyBothGeneral anaesthesiaIntrathecal 25 μg fentanyl + 300 μg morphine50 mgNo50 mgIV PCA morphine + IV paracetamolTables/graphs
 [30]550/50Lower extremity surgeryBothSpinal anaesthesiaIntrathecal 10 mg isobaric bupivacaine + 25 μg fentanyl50 mgNo50 mgIV tramadolTables
 [37]540/40Caesarean deliveryFemaleSpinal anaesthesiaIntrathecal 75 mg lidocaine50 mgNo50 mgOpioids (not specified)Tables
 [32]330/30Lower abdominal and lower limb surgeryBothSpinal anaesthesiaIntrathecal 15 mg hyperbaric bupivacaine50 mgNo50 mgNot specifiedTables
 [38]430/30Caesarean deliveryFemaleSpinal anaesthesia + epidural analgesiaIntrathecal 10 mg isobaric bupivacaine50 mgNo50 mgEpidural bolus of bupivacaine + fentanylTables
Epidural administration of magnesium
 [40]220/20Major abdominal surgeryBothGeneral anaesthesia + epidural analgesiaEpidural 30 mg bupivacaine + 2 mg morphine50 mgNo50 mgIV morphineText/tables
 [14]325/25Total hip arthroplastyBothSpinal + epidural anaesthesiaIntrathecal 7.5 mg hyperbaric bupivacaine + epidural 0.5% bupivacaine as needed50 mg100 mg for 24 h150 mgEpidural fentanyl + oral tramadolText/graphs
 [33]430/30Abdominal hysterectomyFemaleGeneral anaesthesia + epidural analgesiaNone50 mg10 mg.h−1 during surgery + PCEA magnesium 1 mg.ml−1 for 24 h147 mgEpidural bolus of bupivacaine + fentanylText/tablesThree groups included: control; magnesium pre-induction; and magnesium post-surgery. Data from the control and magnesium pre-induction groups were extracted.
 [31]430/30Lower abdominal and lower limb surgeryBothEpidural anaesthesiaEpidural 95 mg bupivacaine50 mgNo50 mgEpidural bolus of bupivacaineText/tables
 [35]320/20Abdominal hysterectomyFemaleEpidural anaesthesiaEpidural 95 mg bupivacaine50 mgNo50 mgEpidural bolus of bupivacaineText
 [39]545/45Caesarean deliveryFemaleSpinal anaesthesia + epidural analgesiaIntrathecal 10 mg hyperbaric bupivacaine + epidural 25 mg bupivacaine + epidural 100 μg fentanyl500 mgNo500 mgIV fentanylText/tables
Intrathecal and epidural administration of magnesium
 [28]140/40Lower limb surgeryBothSpinal anaesthesia + epidural analgesiaIntrathecal 10 mg isobaric bupivacaine + 25 μg fentanyl50 mg100mg.h−1 for 24 h2450 mgEpidural fentanylTables 

Out of the 11 trials that examined intrathecal administration, eight administered a dose of 50 mg (73%) [13, 27, 30, 32, 36–38, 41] and three a dose of approximately 100 mg (27%) [26, 29, 34]. Magnesium was administered epidurally as a single 50-mg bolus in three trials (50%) [31, 35, 40], as a 50-mg bolus followed by 24 h infusion in two trials (33%) [14, 33], and as a single bolus of 500 mg in one trial (17%) [39]. Finally, a single trial administered 50 mg magnesium intrathecally, followed by an epidural infusion of 100 mg.h−1 for 24 h [28]. The total doses administered in 24 h via epidural infusion were 147 mg [33], 150 mg [14] and 2450 mg [28]. There was significant variability between trials in anaesthetic regimens. For example, in the intrathecal space, magnesium was co-administered with levobupivacaine [26], hyperbaric bupivacaine [27, 32, 36], isobaric bupivacaine [29, 30, 34, 38], lidocaine [37] or opioids without local anaesthetic [13, 41].

Table 2 presents the acute pain-related endpoints. The onset of sensory blockade was slower when magnesium was administered in the intrathecal space (mean difference: 2.2 min; 95% CI: 1.0–3.4 min; p = 0.0005), whereas the opposite was true following epidural administration (mean difference: −6.9 min; 95% CI: −8.1 to −5.7 min; p < 0.00001). With intrathecal magnesium, the duration of sensory blockade was longer (mean difference: 23.8 min; 95% CI: 5.6–42.1 p = 0.01), and non-significant trends were noted towards slower onset (mean difference: 1.5 min; 95% CI: −0.3 to 3.3 min; p = 0.10) and longer duration (mean difference: 19.5 min; 95% CI: −1.2 to 40.2 min; p = 0.06) of motor blockade.

Table 2. Acute pain-related endpoints.
   Total number of patients or number of patients with outcome/total number of patients (%)   p value
OutcomeNumber of trialsReferencesMagnesiumPlaceboRR; 95% CIMean difference; 95% CII2; %HeterogeneityOverall effect
Onset time of sensory blockade
 Intrathecal4[29], [36], [30], [32]1501492.2 (1.0–3.4)89< 0.000010.0005
 Epidural2[31], [35]5050−6.9 (−8.1 to −5.7)01.0< 0.00001
 Intrathecal and epidural1[28]40403.5 (2.1–4.9)< 0.00001
Regression time of sensory bockade
 Intrathecal5[27], [29], [36], [30], [32]18017923.8 (5.6–42.1)96< 0.000010.01
 Epidural2[31], [35]50506.0 (−7.0 to 19.0)00.770.37
 Intrathecal and epidural1[28]404010.8 (6.3–15.3)< 0.00001
Onset time of motor blockade
 Intrathecal2[36], [32]60601.5 (−0.3 to 3.3)95< 0.000010.10
 Epidural
 Intrathecal and epidural1[28]40402.3 (1.3–3.3)< 0.00001
Regression time of motor blockade
 Intrathecal7[27], [34], [29], [36], [30], [32]21521419.5 (−1.2 to 40.2)96< 0.000010.06
 Epidural0
 Intrathecal and epidural1[28]40402.5 (−4.2 to 9.2)0.46
Time to first analgesic request after neuraxial blockade; min
 Intrathecal6[27], [34], [29], [36], [30], [37]22522439.6 (16.3–63.0)93< 0.000010.0009
 Epidural4[40], [31], [35], [39]115115109.5 (19.6–199.3)97< 0.000010.02
 Intrathecal and epidural1[28]404018.4 (10.5–26.3)< 0.00001
Morphine consumption at 24 h postoperatively; mg
 Intrathecal4[26], [27], [29], [41]122128−6.0 (−10.4 to −1.6)86< 0.000010.008
 Epidural1[40]2020−7.2 (−9.8 to −4.6)< 0.00001
 Intrathecal and epidural0
Pain scores at 24 h postoperatively at rest
 Intrathecal2[26], [41]5259−1.3 (−5.2 to 2.6)00.440.52
 Epidural1[33]3030−9 (−11.7 to −6.3)< 0.00001
 Intrathecal and epidural0
Pain scores at 24 h postoperatively on movement
 Intrathecal1[41]2929−4 (−7.6 to −0.4)0.03
 Epidural1[33]3030−20 (−26.3 to −13.7)< 0.00001
 Intrathecal and epidural0
Early postoperative morphine consumption; mg
 Intrathecal1[41]29291 (−0.3 to 2.3)0.14
 Epidural0
 Intrathecal and epidural0
Early postoperative pain scores at rest
 Intrathecal2[26], [41]5259−3.3 (−5.6 to −1.0)70.300.005
 Epidural1[33]3030−5.0 (−8.9 to −1.1)0.01
 Intrathecal and epidural0
Early postoperative pain scores on movement
 Intrathecal1[41]2929−3.0 (−6.9 to 0.9)0.13
 Epidural1[33]3030−15.0 (−22.9 to −7.2)0.0002
 Intrathecal and epidural0
Postoperative nausea and vomiting
 Intrathecal9[26], [27], [34], [29], [36], [41], [30], [37], [38]56/313 (26.3%)49/309 (15.9%)1.11 (0.78–1.57)00.620.56
 Epidural4[33], [31], [35], [39]7/125 (5.6%)9/125 (7.2%)0.78 (0.30–2.06)00.960.62
 Intrathecal and epidural1[28]4/40 (10.0%)9/40 (22.5%)0.44 (0.15–1.33)0.15
Pruritus
 Intrathecal7[13], [34], [29], [36], [41], [30], [38]61/238 (25.6%)63/234 (26.9%)0.88 (0.69–1.13)00.540.32
 Epidural3[14], [33], [39]7/100 (7.0%)6/100 (6.0%)1.15 (0.40–3.30)00.880.80
 Intrathecal and epidural1[28]15/40 (37.5%)25/40 (62.5%)0.6 (0.38–0.96)0.03

The time to first analgesic request was increased by 11.1% following intrathecal administration of magnesium (mean difference: 39.6 min; 95% CI: 16.30–63.0 min; p = 0.0009), and by 72.2% after epidural administration (mean difference: 109.5 min; 95% CI: 19.6–199.3 min; p = 0.02). Cumulative morphine consumption at 24 h postoperatively was 29.4% lower with intrathecal magnesium (mean difference: −6.0 mg; 95% CI: −10.4 to −1.6 mg; p = 0.008). There were no differences in other acute pain-related endpoints when trials were grouped for meta-analysis, with the exception of early pain scores at rest following intrathecal magnesium (mean difference: −3.3; 95% CI: −5.6 to −1.0; p = 0.005). The funnel plot for each of these outcomes was inverted, symmetric, and centred around the mean difference on the x-axis, indicating a low likelihood for publication bias.

Only four trials explicitly described monitoring for signs of temporary (headaches, back and leg pain, temporary nerve injury) or permanent paraplegia, quadriplegia, peripheral nerve injuries) neurological complications [27, 30, 32, 38]. Out of the 140 patients included in these trials, only one complication was recorded: rehospitalisation and conservative management for a 4-day persistent headache [27]. There were no differences in the incidences of hypotension, bradycardia or sedation (Table 3). Of note, 39% (7/18) of trials assessed the incidence of hypotension [30, 31, 34, 36–39], whereas only 17% (3/18) assessed the incidence of either bradycardia [30, 31, 38] or sedation [36, 39, 41].

Table 3. Safety-related endpoints.
   Total number of patients or number of patients with outcome/total number of patients (%)  p value
OutcomeNumber of trialsReferencesMagnesiumPlaceboRR; 95% CII2; %HeterogeneityOverall effect
Hypotension
 Intrathecal5[34], [36], [30], [37], [38]39/184 (21.2%)48/181 (26.5%)0.78 (0.55–1.11)00.770.17
 Epidural2[31], [39]24/75 (0.3%)31/75 (41.3%)0.78 (0.57–1.07)00.840.13
 Intrathecal and epidural0
Bradycardia
 Intrathecal2[30], [38]2/80 (2.5%)0/80 (0%)3.00 (0.32–28.21)01.000.34
 Epidural1[31]4/30 (13.3%)6/30 (20.0%)0.67 (0.21–2.13)0.49
 Intrathecal and epidural0
Sedation
 Intrathecal2[36], [41]16/59 (27.1%)21/59 (35.6%)0.49 (0.06–4.08)600.110.51
 Epidural1[39]1/45 (2.2%)0/45 (0%)3.00 (0.13–71.74)0.50
 Intrathecal and epidural0

Discussion

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgement
  7. Competing interests
  8. References

This is the first meta-analysis to assess the analgesic efficacy and safety of neuraxial magnesium administration for postoperative pain management. Intrathecal magnesium increased the time to first analgesic request, reduced morphine consumption at 24 h postoperatively and modestly reduced early postoperative pain scores. When administered in the epidural space, magnesium also increased the time to first analgesic request. These acute pain-related benefits reportedly occur without increased risk of hypotension, bradycardia or sedation. Although the onset of sensory blockade was statistically delayed with the use of intrathecal magnesium, the clinical significance of this result is questionable. Once sensory blockade was established, however, the duration of effect was prolonged. It is difficult to explain this phenomenon given the current understanding of magnesium’s mechanism of action on the central nervous system. It would seem to imply a more direct impact of magnesium on local anaesthetic concentrations or binding within the neuraxis, which has not been previously described. Surprisingly, the opposite effect was observed with epidural administration, resulting in accelerated onset of sensory blockade. The literature does not provide a clear explanation for this observation, but the discrepancy between sites of administration may well be a consequence of the small number of studies available to be included.

In addition to the small number of source studies included in the present review, there was significant heterogeneity, which necessarily limits the generalisability of our findings. For example, trials differed with respect to the type of neuraxial local anaesthetic used, type(s) of neuraxial opioid added, mode of administration, and patient population. Furthermore, the lack of consistency in the reporting of acute pain-related outcomes made it impossible to conduct meta-analyses on several of our pre-defined acute pain-related endpoints.

The dose of neuraxial magnesium that confers optimal analgesia with the fewest possible side effects remains unclear. The earliest clinical trials investigating intrathecal magnesium selected a dose of 50 mg [13]. This was extrapolated from an animal study where 188 μg of intrathecal magnesium potentiated morphine antinociception [11], based on the relative differences between human and rat body weight and cerebrospinal fluid volume. Most of the trials reviewed herein employed doses between 50 and 100 mg, irrespective of whether administered within the intrathecal or epidural space, without providing justification for the doses selected. Only one trial chose an alternate, larger dose of 500 mg for epidural administration. Considering the known differences in pharmacokinetics between intrathecal and epidural local anaesthetics and opioids, it would seem unlikely that the same dose or concentration of magnesium would have equal effects in the intrathecal and epidural spaces.

The lack of reported complications associated with neuraxial magnesium must not be interpreted as an endorsement of its safety, as only four of the 18 trials we reviewed prospectively sought to capture potential neurotoxic side-effects. Animal data have eloquently demonstrated the potential hazards of neuraxial administration of magnesium at similar weight-based doses to the studies included herein (0.7–1.4 mg.kg−1 based on an estimated 70-kg mass). In the only known dose-effect study, intrathecal doses of 0.3 mg.kg−1, 1 mg.kg−1, 2 mg.kg−1 and 3 mg.kg−1 inflicted pain on injection, and produced dose-dependent neurological complications and histological changes in rabbits [15]. Clinically significant motor dysfunction was observed in those rabbits receiving magnesium doses of 2–3 mg.kg−1 and sensory dysfunction increased significantly with increasing doses. These changes were apparent within 1 h of administration and persisted throughout the study period. Furthermore, histological evidence of direct neuronal injury was observed in 22% of animals receiving 1 mg.kg−1 or more. These changes were present 7 days after exposure, but no later observations were taken to determine the long-term consequences of this damage. However, the impact of magnesium on neurological structure and function appears inconsistent between species. Intrathecal doses of 4.6 mg.kg−1 and 9.2 mg.kg−1 of magnesium given every other day to rats over a 30-day period produced no adverse behavioural consequences [42]. The same animals were examined for histological signs of neurotoxicity, revealing no differences from placebo in the 4.6 mg.kg−1 dose group, but confirming a dose-related effect with moderate vacuolation of spinal grey matter ganglion cells in the 9.2 mg.kg−1 group. In a canine model of spinal cord ischaemia, none of the animals receiving intrathecal magnesium doses of 3 mg.kg−1 developed neurological or histological complications following aortic cross-clamping [43]. Taken together, these investigations have not defined the safe dose of intrathecal magnesium but have demonstrated that a risk of clinically relevant neurological injury exists.

In summary, data on the neuraxial administration of magnesium as an analgesic adjunct in the peri-operative setting are promising. However, these results should be interpreted with caution. The lack of neurotoxicity assessment in most clinical trials, combined with current limited animal data, has not yet defined the risk of neurological complications resulting from neuraxial magnesium. Additional dose-effect studies would strengthen our understanding of the safety profile of neuraxial magnesium before translation into routine clinical practice can be supported.

Acknowledgement

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgement
  7. Competing interests
  8. References

We are grateful to Dr Saravanan Ankichetty for his assistance in the preparation of this article.

Competing interests

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgement
  7. Competing interests
  8. References

EA has received grants from the Swiss Academy for Anaesthesia Research (SACAR), Lausanne, Switzerland and from the ‘Foundation SICPA’, Prilly, Switzerland.

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  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgement
  7. Competing interests
  8. References
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