Unexpectedly feeling blue: unforeseen desaturation during anaesthesia
James Watts and T Aji-Mathew highlight drawbacks associated with the use of chemical dyes during anaesthesia
Dyes are commonly used as adjuncts during various types of surgery; however, they are not merely inert chemicals, and are associated with a variety of pharmacological and biological reactions [1,2].
A young ASA 1 woman presented following chemotherapy for a mastectomy and axillary node clearance. Anaesthesia was induced using propofol, lignocaine, midazolam and fentanyl, and maintained using desflurane and atracurium. Morphine, paracetamol and voltarol were administered intravenously for pain relief, and the patient was ventilated through a laryngeal mask airway.
Just after surgery commenced, the patient’s oxygen saturation dropped within a matter of seconds to 72 per cent, and 100 per cent oxygen was administered. End-expiratory CO2 levels were maintained, and there was no change in airway resistance, tidal volume or cardiovascular parameters. Auscultation of the chest was normal. Oxygen saturation levels slowly rose, but settled at about 83 per cent.
Blood gases confirmed an essentially normal result, with values of: pH 7.445, pCO2 4.4, PO2 55.68, bicarbonate 22.2 and a base excess of BE -1.29. The estimated oxygen saturation from the gas analysis was 100 per cent. Lactate was confirmed to be 1.2, and the rest of the blood results were normal; however, the patient’s methaemaglobin level was found to be 9.2 per cent.
The onset of the event had rapidly followed the subcutaneous injection of 1.5ml methylene blue in the breast in order to identify the draining lymph nodes. The anaesthetist involved was well aware that administration of small amounts of methylene blue could reduce recorded oxygen saturation levels, but was used to this phenomenon occurring slowly over time. It was concluded that some of the dye must have been injected intravenously in this case, accounting for the rapid onset.
Surgery continued uneventfully without further intervention. Over two hours, oxygen saturation recovered, to the point where it was 98 per cent on air in recovery. After a period of observation, the patient was discharged home.
Chemical dyes in anaesthetic practice
Methylene blue is one of a series of blue, purple and green dyes (e.g. gentian violet, isosulphan blue, methylene green) that have been used in medical practice over the years. An anaesthetist will commonly encounter them during surgery – where they are used to stain or identify tissue (lymph nodes, parathyroid glands, etc.) or to confirm the patency of a hollow viscus (e.g. fallopian tubes). They are not inert chemicals, however, and as anaesthetists we should be aware of the problems that may arise from their use
Methylene blue is a heterocyclic aromatic organic compound with the formula C16H18N3SCl, and is presented as a powder that is reconstituted with water. Although stable at normal room temperatures, it is known to be flammable. It is known to cause skin and eye irritation if it comes into direct contact due to its acidic pH. Side-effects include non-specific phenomena such as nausea, vomiting, abdominal pain, hyperpyrexia and dizziness. It can also cause discolouration of patient skin, and can in some cases lead to tattooing of tissues. It has mild monoamine oxidase inhibitory activity and may precipitate hypertension, and in some cases can interact with serotonin reuptake inhibitors, giving rise to serotonin syndrome, which is characterised by delirium, aphasia, disorders of muscle tone, and impaired consciousness [3–6].
This MAOI type effect has been proposed as a possible adjunct to treating hypotension in sepsis, although it has not been widely adopted ,
Like all chemicals, methylene blue can be associated with anaphylaxis. It is thought that the incidence is lower than some other blue dyes (e.g. isosulphan blue), hence its ubiquity in surgical practice. Overall incidence may be 0.8–2.8 per cent, but in 86 per cent of cases when anaphylaxis occurs it may be delayed – this means that following short surgical procedures, it is possible that anaphylaxis may occur in the recovery area. Previous medical exposure is not necessary to predispose to this happening because of the wide distribution of similar chemicals in everyday life; however, such anaphylaxis does seem to respond well to standard treatment, and there is a suggestion that the use of smaller volumes of dye may reduce the incidence of such reactions [8–13].
In addition, methylene blue may precipitate haemolytic anaemia in some patients with enzyme disorders (e.g. G6PD) . It is also reported to have a variety of antimicrobial properties, including activity against malaria, parasites, viruses and bacteria, and has been used as an adjunct to treating skin conditions and some cancers [15–19].
Methaemoglobinaemia is a condition where normal haemoglobin contains an Fe3+ (ferric) ion rather than an Fe2+ (ferrous) one, with a subsequent reduction in oxygen carriage capacity. It can be caused by exposure to a variety of drugs and chemicals, or can be congenital due to enzyme deficiency. It manifests when methaemoglobin levels are greater than one per cent. Methylene blue reduces the Fe3+ ion back to the ferrous state, and should be used where the patient is symptomatic, or when the methaemoglobin level is greater than 20 per cent. It is given in a dose of 1–2mg/kg (up to a total of 50mg in adults, adolescents and older children) as a one per cent solution in IV saline over 3–5 minutes. Administration may be repeated at 1mg/kg every 30 minutes as necessary to control symptoms, although caution is required as doses of about 7mg/kg can cause significant methaemoglobinaemia. The treatment is otherwise supportive [20–23].
Gentian violet (also known as crystal violet; [C(C6H4N(CH3)2)3]Cl) has extensive antimicrobial and antiparasitic properties, and has been used for treating oral thrush and MRSA [24–26].
Patent blue V (C27H31N2O7S2.0.5Ca) and isosulfan blue (C27H31N2NaO6S2) are similar dyes. Unlike methylene blue they are taken up by proteins in the lymph rather than capillaries and can be used to map lymphatic drainage. They have also been associated with anaphylaxis [27–29].
Methylene green (C16H17ClN4O2) and malachite green are now used mainly for tissue staining in the laboratories, but are also known to have antimicrobial properties.
Other dyes that are used in medical practice can have similar effects, and anaesthetists should also be aware of the potential effects of fluorescein. This orange dye is commonly used to stain the sclera to identify injury; however, it is also used intravenously by our ophthalmic colleagues for retinal artery mapping. The dye has an associated anaphylactic rate of approximately 1–6 per cent, and so it is possible that as anaesthetists we may be called to their wards or imaging departments to assist in treating such a reaction.
James Watts and T Aji-Mathew are both consultants in anaesthesia at East Lancashire NHS Hospitals Trust in Blackburn
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