Dear Editor

Maxwell-Armstrong et al[1] have apparently done a significant amount of work in sampling the current state of knowledge among haematology technicians on the performance of Diagnostic Peritoneal Lavage (DPL) analysis. They also report on surgeons’ experience of the procedure. Their analysis and conclusions, however, seem not to be supported by this data. Indeed, their paper climaxes with propositions relating to the use of ultrasound, for the relative superiority of which they have collected as much evidence as for fortune-telling.

Despite my own high level of interest in the use of ultrasound, I cannot but disagree with the methods used by the authors in analysing the use of its “rival” – DPL.

The authors surveyed technician’s experience in the analysis of DPL specimens and this was found apparently lacking. They then still accepted these same technicians’ opinions about how this procedure is or should be performed. They question the fine details of which fluid is used and in which container it is send when a surgeon would struggle to find a fluid or container which would be inadequate regardless of what the technician knew of this. And I would not trust an estimate of an hour to analyse a sample – it is likely that this was received from those less experienced technicians who were merely guessing.

To suggest that an investigation be abandoned because it is not as available as one would like is irresponsible. Only a few years ago, one would have envied such a level of accessibility to, say, CT scanning for head injuries or cardiac enzymes for chest pain, as has been identified herein for DPL. Gratefully, we did not abandon the use of CT then for these reasons. It would only take a minimal investment to reach an acceptable level of knowledge and protocols in labs.

As for surgeons’ experience, the data presented was poorly representative (48% response) and poorly analysed. To claim that there is little increase in experience with duration in post is misleading. A closer look at their own data would have reassured the authors. For example, 51 of 54 consultants with fewer than 2 years’ experience performed DPL (94%) – an average of 47% per year of work. The figure is 282 of 333 (85%) for those with over 10 years’ experience, which, assuming 10-25 years of practise in this group, is 3.4-8.5% per year worked. Ignoring pre-consultant exposure for both groups, this shows recently trained consultants are around 10 times more likely to perform DPL per year of practise and will thus be more experienced by the time they have 10 years behind them.

No comparative figures were presented on surgeons’ experience in the performance of ultrasound or on the availability of other trained users and the costs involved in ultrasound equipment and training. To reach competence (and hence sensitivity) in the use of ultrasound is certainly more time-consuming and costly than to perfect the use of DPL. In addition, the ATLS guidelines referred to in the article were compiled primarily for physicians working in smaller set-ups, not for the “major units” surveyed. In the latter, most patients will have CT scans unless unstable enough to need immediate surgery.

Despite the problems presented by ultrasound in the circumstances of suspected intra-peritoneal haemorrhage – operator inexperience/unavailability, obese or previously operated patients, subcutaneous air, etc. – it is still probably worthy of attention. But our approach must be scientific.

References

(1) Maxwell-Armstrong C, Brooks A, Field M, Hammond J, Abercrombie J. Diagnostic peritoneal lavage analysis: should trauma guidelines be revised. Emergency Medicine Journal 2002;19(6): 524-525.

Dear Editor,

Article named Lower limb amputation with CPR in progress: recovery following prolonged cardiac arrest(Ref1) is very interesting as well as thought provoking. Such clinical scenario is not only rare but needs a good team effort to come to a clinical judgement. Amputation in acute scenario in the absence of obvious vascular injury is definitely a brave decision.

I would be grateful for the authors if my doubts can be clarified

1) There are many causes of hyperkalemia and how the team treating could come to a conclusion that the hyperkalemia was caused by the rhabdomyolysis of foot.

2) Drugs like cocaine, heroine can cause rhabdomyolysis (of any muscle), disseminated intra vascular coagulation, hyperkalemia and arrythmias which can be made worse by naloxone (Ref2). In the presented clinical situation these possibilities cannot be ruled out.

3) Arterial blood gas values of this patient would be very interesting to see as well, with particular emphasis on acidosis and anion gap.

4) If limb ischaemia and reprfusion of the ischaemic limb are considered as the cause of hyperkalemia, application of tourniquet or clamping of the vessels can act as diagnostic test rather than going for an amputation.

5) What are the parameters that the teams used to determine the level of initial amputation and what was the initial level of amputation.

Thanking you

Yours sincerely

Mr Sreenadh Gella
SPR Orthopaedics
Calderdale Royal Hospital

Reference

1. R Wise1, I Higginson2, J Benger2 and N Rawlinson1 Lower limb amputation with CPR in progress: recovery following prolonged cardiac arrest, Emergency Medicine Journal 2006;23:e20; doi:10.1136/emj.2005.

2. McCann B, Hunter R, McCann J. Cocaine/heroin induced rhabdomyolysis and ventricular fibrillation.Emerg Med J. 2002 May;19(3):264-5.

Dear Editor

While I normally find the Best BETs both informative and useful, I was surprised at the publishing of one concerning gastric lavage in drug overdose [1].

Gastric lavage is both dangerous and without benefit in all but a few overdoses. The 1997 Joint Position Statement made by the American Academy of Clinical Toxicology, and the European Association of Poisons Centres stated that gastric lavage should never be routinely used [2].

A statement on the National Poisons Information Website (TOXBASE) indicates that gastric lavage should only be considered in a case of a potentially life-threatening overdose taken within the last hour of a poison that is not adsorbed by charcoal.

To state that gastric lavage is no better than charcoal as a clinical bottom line at reducing toxicity following aspirin or non-steroidal anti- inflammatory drugs is at Best misleading.

References

(1) Teece S. Gastric lavage in aspirin and non-steroidal anti- inflammatory drug overdose. Emerg Med J 2004;21:591-592.

(2) American Academy of Clinical Toxicology and European Association of Poisons Centres. Gastric Lavage. J Clin Toxicol-Clin Toxicol 1997;35:711-719.

Dear Editor,

The considerable pain caused by common partial thickness cutaneous burns is widely acknowledged to be a difficult therapeutic problem. Growing evidence has shown peripheral opioid receptors to be a potentially exploitable target for topical analgesic intervention. The efficacy of topical opioids at various time points following burns, and the relative effectiveness of their use for various burn depths remains to be elucidated, so we welcome Welling’s contribution to this field.

We work within a large burns service, and have used 10 to 30mg of topical morphine on a selection of burn wounds for over a year, mixing it primarily with Flamazine® cream. Thus far, we have been impressed by its efficacy and the longevity of its action. In our hands however, its use has been confined to cases responding poorly to conventional systemic analgesic regimes and has therefore rarely seen use as early in the post- burn period as the scenario described by Welling’s study.

Interpretation of published burns research is unfortunately often compromised by disparity in nomenclature pertaining to burn depth. Unfortunately, as the study’s title alludes, this is also true in this study. During Peter Shakespeare’s editorship of the International Journal of Burn Care, he attempted to standardise this nomenclature to the anatomical definitions of:

• superficial (epidermis only)

• superficial partial thickness (epidermis & superficial dermis)

• deep dermal partial thickness (epidermis & deeper dermis)

• full thickness

“Partial thickness” essentially refers to all burns less than full thickness, and therefore in itself is inadequate to describe burn depth. It is unclear from the published study what depths of burns have been included. Elucidation of burn depth warrants further attention, as it may correlate with the efficacy of topical morphine, because where the epidermis is retained (superficial burns) this may provide a barrier to topical absorption. Also, the deeper the burn, the greater the oedema and the worse the vascularity, which is likely to influence tissue penetration and the bioavailability profile. Furthermore, the absorption of morphine through glabrous skin (palms & soles) is likely to be considerably impaired and we would anticipate hand burns to have made a substantial contribution to the subjects studied, but no distinction has been made.

There are certain problems we commonly see with burns treated by non- specialists. Firstly, there is inadequacy of burn debridement; all blisters should be removed, as they represent an infection risk. Admittedly, at first attendance in A&E, they are often initially absent or incompletely formed, complicating this first assessment. This problem should be approached by rubbing the burned area with gauze to mechanically shear off the roof of blisters-to-be. This is required if TBSA is to be correctly assessed (purely superficial burns are excluded from TBSA assessment). Failure to debride blisters will present a considerable barrier to absorption of topical analgesics (epidermis + thick fluid layer). It may be the case that such burn assessment and debridement was performed, but simply not reported.

Following thorough debridement and wound toilet, any burn deeper than superficial depth which is not being directly referred for specialist management should be dressed with antimicrobial dressings. The rate of infection in burns treated without topical antimicrobials (or inadequately debrided) is unacceptably high and this carries the consequence of increasing burn depth, delaying healing, worsening scarring and increases the proportion of burns requiring skin-grafting. This common misconception is in part attributable to advice given by burns services, who generally prefer the omission of topical antimicrobials in cases they have been referred, so that on admission the wound surface is not obscured by such substances (however antimicrobials are then applied after assessment). The omission of topical antimicrobials to burns should be the exception, not the rule, and is reserved almost exclusively for cases experiencing hypersensitivity to such agents. Paraffin tulle dressings are now falling from favour due to a high incidence of adherence to the burn wound and granuloma formation. Favoured alternatives include the silicone based Mepitel® and lotion impregnated Atrauman® dressings. Six-layer Jelonet® dressings are not to be recommended, as at this thickness they are relatively impermeable, compromising the function of the dressing. We therefore take exception to the dressings chosen for the study.

The study unfortunately has no statistically significant findings, in part due to inadequate subject inclusion, failing to meet the calculated requirement of 21 subjects in each arm of the study. The results of the visual analogue pain scores are compromised by systemic analgesia administration not having been standardised. However, all subjects received paracetamol and/or ibuprofen at admission, and assessment of the VAS over the duration of action of these analgesics is therefore the least biased. Over this period, the morphine group was the only group to see a VAS reduction of >20mm on two consecutive time intervals and overall, the VAS for the morphine group fell to 30% of its pre-treatment value, compared to 43% and 40% for the other two groups. Whilst this does not reach statistical significance, this is likely attributable to inadequate numbers rather than an absence of therapeutic effect. The finding closest to reaching statistical significance was of subjects in the morphine group requiring less analgesia after discharge.

The results presented in Table 5 summarise the total analgesic units for each group; the topical morphine has also been attributed analgesic units for each subject and this included in the final analysis. We would argue that to test the hypothesis of whether topical morphine works topically on fresh burn wounds, this treatment arm should not be attributed these additional analgesic units as their effect as analgesia is unproven and this is what is on test. This amendment would lend support to the hypothesis that topical morphine is effective in burn wounds as other studies have shown.

Previous work includes the cited pilot study by Long , in which subjects <72h following <25% TBSA burns were divided into two treatment arms, each comprising two patients. One arm received morphine infused silver sulfadiazine cream, whilst the control arm received plain silver sulfadiazine cream. Twice daily dressing changes using these compounds occurred twice daily for 4 days, but none of the patients remained in the study until its conclusion. The study found pain levels and anxiolytic usage to be reduced, but was limited by small study size.

More recently, Robertson showed peripheral opioid receptor stimulation by fentanyl is opposed by naloxone in healthy subjects with standardised experimental burns. Volunteers’ bilateral forearm burns had saline subcutaneously injected on one side and naloxone on the other. Heat pain threshold and mechanical pain ratings were found to be similar at the two sites. Subsequently, fentanyl was injected at both sites, and following this, heat pain threshold was increased and mechanical pain decreased at the site without naloxone. This gives further evidence of the presence of peripheral opioid receptors very shortly after burn injury.

The bioavailability of topical opioids applied to burn wounds remains unclear. Ribeiro’s work on topical morphine in cutaneous ulcers showed poor bioavailability, with plasma penetration only demonstrable in 17%, and this at only 20% of the administered dose . In the canine model, morphine applied to peri-articular intact skin does not achieve measurable plasma penetration, although after 2 – 4 hours it is measurable in urine and synovial fluid in half of subjects . In view of burn eschar and burn related hyperaemia, these findings are not necessarily transferable to the burn scenario. Furthermore, the optimum opioid for such topical administration remains unknown, morphine sulphate has a relatively poor absorption profile, which diamorphine improves upon, or indeed the enhanced lipophilicity of fentanyl may be exploited to ensure better penetration, but this may sacrifice duration of action.

The potential for targeting of peripheral opioid receptors as a locus of pain control early in the course of cutaneous wounds has been established. It remains to be conclusively proven that topical morphine is effective on burns, and from what time point this is effective, as it is uncertain how long opioid receptors take post-injury before they appear in peripheral tissues, though “minutes to hours” has been quoted by Stein, who has carried out much research into peripheral opioid receptors . From the results of Robertson’s study, it is likely that topical opioids are an appropriate intervention as early as the first dressing. It also remains to be elucidated what is the most appropriate opioid, at what dose, and what nuances exist within specific wounds such as burns (efficacy in different burn depths, duration of action etc.). Welling’s study is a welcome addition to the sparse research in this area, although we would interpret her results differently and urge reconsideration in the choice of burn dressings used.

1. Shakespeare PG. Standards and quality in burn treatment. Burns. 2001; 27(8): 791-792

2. Long TD, Cathers TA, Twillman R, O’Donnell T, Garrigues N, Jones T. Morphine-infused silver sulfadiazine (MISS) cream for burn analgesia: a pilot study. Journal of Burn Care and Rehabilitation. 2001; 22(2): 118-123

3. Robertson LJ, Drummond PD, Hammond GR. Naloxone antagonizes the local antihyperalgesic effect of fentanyl in burnt skin of healthy humans. The Journal of Pain. 2007; 8(6): 489-493

4. Ribeiro MDC, Joel SP, Zeppetella G. The bioavailability of morphine applied topically to cutaneous ulcers. Journal of Pain and Symptom Management. 2004; 27(5): 434-439

5. Moore DP, Parikh R, Vernick SH, Petroski GF, Pryor WH, Kazmierczak SC. Topical morphine in a canine model: a pilot study. Archives of Physical Medicine and Rehabilitation. 1998; 79(9): 1034-1037

6. Stein C. The control of pain in peripheral tissue by opioids. New England Journal of Medicine. 1995; 332(25): 1685-1690