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Summary

  1. Top of page
  2. Summary
  3. Method
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
  8. Appendix

There is evidence that administration of lipid emulsion improves outcome in cardiovascular collapse secondary to local anaesthetic toxicity. We sent a questionnaire to the lead consultant anaesthetist in every consultant-led labour ward in the UK asking about local guidelines for treatment of cardiac arrest, and whether or nor lipid emulsion was available on the labour ward and included in the guideline. We received replies from 195 (86%) labour wards. One hundred and seven (55%) reported having a guideline for the treatment of cardiovascular collapse secondary to local anaesthetic toxicity. Of these guidelines, lipid emulsion was included in 78 (40%). Lipid emulsion was readily available on 95 labour wards (49%). Of the remaining units, there were plans to make lipid available in the near future in 46 (46%). Of the 95 labour wards where lipid emulsion was readily available, 80 (84%) had a recommended dose regimen for its administration. Around three-quarters of labour wards in the UK either have lipid emulsion available or plan to obtain it. This uptake should ideally be 100%.

Inadvertent intravenous injection of long-acting amide local anaesthetic is a rare but potentially devastating complication of regional and central neuraxial anaesthesia. Cardiovascular collapse following accidental intravenous administration of bupivacaine in particular is extremely difficult to treat using standard resuscitation drugs, and the mortality in this situation is high. Since the withdrawal of bretylium, there has been no drug available for specific treatment of local anaesthetic toxicity besides standard resuscitation drugs.

There is evidence that administration of intravenous lipid emulsion improves outcome in local anaesthetic-induced cardiac arrest in animals [1, 2]. Interest in the use of lipid emulsion for this indication has been high in recent months and the literature now contains a number of reports of the successful use of lipid emulsion in resuscitation from local anaesthetic-induced cardiac arrest in humans [3–5].

It has been recommended that where large bolus doses of local anaesthetic are routinely administered, lipid emulsion should be readily available [6]. The labour ward is one such area. The large number of epidurals sited or topped up for Caesarean section each year means the possibility of inadvertent intravascular injection of local anaesthetic is always present.

This questionnaire survey of labour wards throughout the UK was designed to gauge the current degree of provision of lipid emulsion, as well as to ascertain whether units had guidelines for its use.

Method

  1. Top of page
  2. Summary
  3. Method
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
  8. Appendix

We sought and gained approval from the audit subcommittee of the Obstetric Anaesthetists' Association, who approved the content of the survey questionnaire and provided us with contact details for the lead obstetric anaesthetists in each consultant-led labour ward in the UK. As well as questions relating to the availability or otherwise of lipid emulsion, the questionnaire also asked whether there had been any recent case of local anaesthetic-related cardiovascular collapse and whether the anaesthetists in the unit employed a test dose to rule out intravascular catheter placement. The approved questionnaire is attached in Appendix 1.

We sent out the survey questionnaire with a covering letter and a prepaid envelope to all 226 lead obstetric anaesthetists in the UK during February 2007. These were marked to allow non-responders to be contacted; all data were treated anonymously. In May 2007, we sent a second mailing of the survey to non-responders. The data were analysed in Microsoft®excel (Microsoft, Seattle, WA, USA).

Results

  1. Top of page
  2. Summary
  3. Method
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
  8. Appendix

Of the 197 returned questionnaires, two were incomplete and disregarded in the further analysis. This left 195 for analysis, a response rate of 86%.

Nine units (5%) reported an incident of cardiovascular collapse secondary to local anaesthetic toxicity within the last 5 years. Sixty-two units (32%) had a test dose designed to exclude intravascular epidural catheter placement; some units reported more than one test dose. The drugs used varied widely. Forty-four labour wards used bupivacaine in concentrations ranging from 0.1% to 0.5% and volumes ranging from 2 ml of 0.5% to 15 ml of 0.1%. Of these units, 18 added fentanyl to the bupivacaine, one added alfentanil and one added adrenaline. Eleven units used lidocaine 2%, ranging from 2 to 4 ml and two added adrenaline to the lidocaine. Five units used levobupivacaine in concentrations ranging from 0.1% to 0.5%. One unit reported ‘the first dose is the test dose’ and two reported ‘every dose is a test dose’.

Of the responding units, 107 (55%) reported having an algorithm or guideline for the treatment of cardiovascular collapse secondary to local anaesthetic toxicity and lipid emulsion was included in the algorithm in 78 (40%) labour wards.

Lipid emulsion was readily available on 95 labour wards (49%). Of the 100 units that did not have lipid immediately available, there were plans to make it available in the near future in 46 (46%). Reasons why the remaining units were not planning to make lipid emulsion readily available are shown in Table 1. Some units offered more than one reason, hence the numbers add up to more than the expected 54.

Table 1.   Reasons given for the unavailability of lipid emulsion on the labour ward.
Reasonn (%)
  1. AAGBI, Association of Anaesthetists of Great Britain and Ireland.

Unconvinced by need27 (39%)
Unconvinced by the evidence11 (16%)
Unaware of the research9 (13%)
Logistical reasons6 (9%)
No epidural service4 (6%)
Lack of funding4 (6%)
Can get from nearby clinical area4 (6%)
Not yet discussed in unit2 (3%)
Inertia1 (1%)
Awaiting AAGBI guidance1 (1%)

Of the 95 labour wards where lipid emulsion was readily available, 80 (84%) had a recommended dose regimen for its administration. Interestingly, 13 of the units where lipid emulsion was not readily available also had such a regimen. Sixty units supplied a copy of their administration regimen, and broadly there were two dose regimens used. Thirty-seven units had prepared an administration protocol based on Weinberg's original recommendations, as publicised in an editorial [6]. Twenty-two units used the more up-to-date recommendations from Weinberg's team, mostly gained from the website http://www.lipidrescue.org. One unit's protocol consisted of the rapid administration of an entire bag of lipid emulsion while advanced life support was ongoing, followed by an infusion of a further bag if a perfusing rhythm was not restored. It was not stated where this regimen originated.

Discussion

  1. Top of page
  2. Summary
  3. Method
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
  8. Appendix

The survey has shown that, as of May 2007, almost half of consultant-led labour wards in the UK have lipid emulsion readily available for use in the event of cardiovascular collapse secondary to local anaesthetic toxicity. Of the remainder, just under half report the intention to make it available in the near future. The remaining units gave reasons as to why it was felt that immediate availability of lipid emulsion was unnecessary. The most common reason given, ‘unconvinced by need’, is perhaps based on the perception of the rarity of inadvertent intravenous local anaesthetic administration. Although this is indeed rare, it is a complication that can occur despite scrupulous technique and often has fatal consequences, so any method of decreasing the mortality and morbidity associated with this should be fully embraced.

The second most common reason for not making this drug available was being ‘unconvinced by the evidence.’ Research in this area is limited as it is not possible to perform ethical randomised controlled trials on humans, and animal trials have their limitations. Proof of the efficacy of lipid in treating local anaesthetic toxicity in humans will therefore come from case reports and, given the rarity of this adverse event, it will be some time before a large body of evidence is available. Recent months, however, have shown a spate of reported cases of successful resuscitation in humans using lipid emulsion, with three cases published in peer-reviewed journals [3–5] and a number of other cases reported to the website http://www.lipidrescue.org[7]. As yet, there have been no reports of the unsuccessful use of this substance, nor any of significant complications and, as such, lipid should be considered promptly in a case of cardiac arrest secondary to local anaesthetic toxicity if there has been no response to standard resuscitation measures.

There are no reports to date of maternal resuscitation with lipid emulsion, and therefore it is not known what effect, if any, a large bolus of lipid will have on the fetus. There are no data even from animal studies in this area. Theoretically, the bolus of lipid will freely cross the placenta and enter the fetal circulation in a high concentration. There are reports of reversible pulmonary complications following lipid administration in a study looking at the feasibility of lipid emulsion as a carrier for amphotericin in adult neutropenic patients [8]. It is therefore possible that babies born after successful maternal resuscitation may be at risk of developing pulmonary complications secondary to the lipid load, as may the mothers themselves. However, both maternal and fetal outcome are likely to be worse following an unsuccessfully treated episode of cardiovascular collapse. The decision to deliver the baby by emergency Caesarean section should be made quickly to maximise the chances of a successful outcome, but preparations for operative delivery must not compromise maternal advanced life support or delay the administration of lipid.

Nine of the respondents reported an incident of local anaesthetic-related cardiovascular collapse within the last 5 years. Of these labour wards, four already have lipid available and four are planning to get it. Therefore, a higher proportion of units with recent experience of this complication have, or are in the process of acquiring, lipid emulsion (89% vs 76% of units with no recent experience). This may be because the recent experience has led the departments involved to focus on ways to reduce the consequences of a further event.

Much has been made in correspondence of prevention being the key where this complication is concerned [9] and this is, of course, the case. One respondent to this survey claimed the need for lipid meant unsafe practice as toxic plasma concentrations should not be reached if bupivacaine is given slowly in small aliquots, but unfortunately there is always the potential for human error, and intravenous injection can occur despite negative test doses and negative aspiration.

We also asked about the use of test doses to attempt to gain an understanding of what is being done nationally. It is apparent from the disparate responses that there is no consensus on whether to use a test dose, or what to use. We were specifically interested in the use of a test dose to exclude intravascular catheter placement. Perhaps the range of responses is indicative of the fact that there is no universally accepted way of reliably determining intravascular placement [10]. A small dose of local anaesthetic by itself is unlikely to cause symptoms, and whereas the addition of adrenaline to the local anaesthetic may cause a detectable tachycardia, only three units reported that they routinely use such a mixture. The possibility of catheter migration after insertion is always present and so the best advice, specifically mentioned by only two units, is to treat every dose as a test dose.

Most labour wards with lipid had a suggested regimen for its administration, and largely these were based on two versions of a regimen initially suggested by Weinberg and colleagues [1]. These two dose regimens differ primarily in the volume of lipid given as a bolus: 1 mg.kg−1 from the original recommendations, increased to 1.5 mg.kg−1 following further experimentation (Weinberg G, personal communication, April 2007). Given that lipid emulsion will be used rarely, all units where lipid is available should have a defined administration protocol in order that the minimum delay occurs in its administration should it be required. It makes sense to use the most up to date recommendations, bearing in mind that these are likely to change as further experiments are performed and further cases reported.

There are a number of problems with this survey. As with any survey, it is subject to responder bias. However, the fact that we surveyed every labour ward in the UK and achieved a response rate of 86% should mean that the results are as representative as possible. We made no assessment of the availability of lipid emulsion in other areas such as theatre complexes, emergency departments or intensive care units. It is possible that the uptake in these departments mirrors that of labour wards, but we cannot conclude this with any certainty from the survey as performed. This is also a rapidly changing area of research, which has attracted a great deal of interest among the anaesthetic community in general. As the number of case reports of the successful use of lipid increases, there is likely to be an increase in the national availability of this drug.

It is possible that there are adverse effects of lipid emulsion used in this context, and that these will emerge in future case reports. However, the limited evidence available in humans currently shows this to be a treatment with minimal side-effects and remarkable efficacy. Adverse effects of lipid emulsion would have to be severe indeed to recommend not using it to treat a condition that, without lipid, is almost invariably fatal.

At the time of going to press, the Association of Anaesthetists of Great Britain and Ireland has produced a guideline for the management of severe local anaesthetic toxicity, based on the use of lipid emulsion [11]. This endorsement is likely to increase the nationwide availability of this drug.

We have shown that around three-quarters of labour wards in the UK either have lipid emulsion available or plan to obtain it. Given the unpredictable nature of intravenous local anaesthetic toxicity, this uptake should be higher, ideally 100%. As the evidence base for lipid increases, there may come a point where it could be considered negligent not to have lipid emulsion available should a patient suffer the rare complication of cardiac arrest secondary to local anaesthetic toxicity.

Acknowledgements

  1. Top of page
  2. Summary
  3. Method
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
  8. Appendix

We would like to thank the consultant obstetric anaesthetists across the United Kingdom who took the time to return our questionnaire. We are also grateful to Dr Philip Barclay for his advice on the initial draft of the questionnaire.

References

  1. Top of page
  2. Summary
  3. Method
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
  8. Appendix

Appendix

  1. Top of page
  2. Summary
  3. Method
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
  8. Appendix

Appendix 1

inline image

This survey has the OAA ‘Seal of Approval’

Survey No. 68, approved December 2006.

Availability of lipid emulsion in obstetric anaesthesia

As far as you are aware, has there been any incident of cardiovascular collapse secondary to local anaesthetic toxicity in your unit within the last 5 years?

Yes []  

No []

Does your unit have a test dose designed to detect intravascular catheter placement?

Yes []  

No []

If YES, what is used in the test dose?

Does your unit have an algorithm/guideline for the treatment of cardiovascular collapse secondary to local anaesthetic toxicity?

Yes []  

No []

If YES, does this algorithm/guideline include the use of lipid emulsion?

Yes []  

No []

Are bags of lipid emulsion (for example Intralipid®) readily available within your unit?

Yes []  

No []

If NO, are there any plans to make bags of lipid emulsion readily available?

Yes []  

No []

If NO, what is/are the reason(s) for this?

Unconvinced by evidence []

 Unconvinced by need []

 Lack of funding []

 Logistical reasons []

 Unaware of the research []

 Other []

If your unit DOES have lipid emulsion available, is there a suggested dose regimen for its administration?

Yes []  

No []

 (if YES, it would be useful if you could include a summary of this with your reply.)

Many thanks for taking the time to complete this survey. If you have further comments, please add them below. Please then return this form in the stamped addressed envelope supplied.

Thank you.