Annabelle SJ Baughan [1] MB FRCP FRCPath,
Deborah Cavel-Greant [1],
Janice Megalo [1] AAS-MAA, and
Frank Weber [2] MD PhD.
[1] Periodic Paralysis International (www.hkpp.org)
[2] Colonel, Medical Service (Neurology), German Air Force. Military Hospital (Bundeswehrkrankenhaus), 89081 Ulm, & German Air Force Center of Aerospace Medicine, D-82256 Fürstenfelbruck. Medical Adviser, Periodic Paralysis Association;
Corresponding author: ASJ [email protected]
With grateful acknowledgement to members of the private Listserv at Periodic Paralysis International (www.hkpp.org) and members of the Periodic Paralysis Association (www.periodicparalysis.org) who have contributed much of the anecdotal evidence
Part 2: ‘Practical guidelines’ – separate document at www.hkpp.org
Parts 1 and 2 share the same Introduction. and Reference List
The combined reference list for both Part 1 and Part 2 is attached to each document
CONTENTS
Introduction
Elective (non-emergency) surgery in patients with Periodic Paralysis Disorders
Definitions
General points
Pre-admission: doctors and other healthcare staff
Pre-admission: patients
Admission to hospital: patients
Peri-operative management: overriding principles
Peri-operative management: general points
Peri-operative management: classical triggers and their management
Applicable to all patients with a Periodic Paralysis Disorder
Hypokalaemic periodic paralysis
Hyperkalaemic periodic paralysis
Andersen-Tawil Syndrome
The Potassium Aggravated Myotonias including Paramyotonia Congenita (von Eulenburg)
Emergency surgery
Introduction
The primary Periodic Paralysis Disorders (PPDs) comprise a group of related rare genetic ion channelopathies affecting muscle fibre membranes in voluntary muscle [1, 2, 3]. Affected patients have symptoms which vary in severity – both between patients (even within the same kindred) and in the same patient at different times – but are defined by intermittent acute attacks of flaccid paralysis of voluntary muscles, sometimes milder acute muscle paresis, and with or without myotonia. The currently defined forms of genetic Periodic Paralysis (derived from Jurkat-Rott and Lehmann-Horn [4] are shown in table 1.
Table 1: Nomenclature of Periodic Paralysis Disorders
Abbreviation Mutated Gene * Name
Hypo1PP CACNA1S Hypokalaemic Periodic Paralysis Type 1
Hypo2PP SCN4A Hypokalaemic Periodic Paralysis Type 2
Hypo3PP KCNJ18 Hypokalaemic Periodic Paralysis Type 3
HyperPP SCN4A Hyperkalaemic Periodic Paralysis
NormoPP SCN4A Normokalaemic Periodic Paralysis
ATS KCNJ2 Andersen-Tawil Syndrome
TPP KCNJ18 Thyrotoxic Periodic Paralysis
PMC SCN4A Paramyotonia Congenita
PAM SCN4A Potassium Aggravated Myotonia
* Many diagnosed individuals have a documented gene mutation (the incidence varies with the particular disorder). Other patients have been clinically diagnosed with a phenotypically identical disorder but a genetic mutation has not been identified to date. With the current state of knowledge, patients with so-called PP Disorders should be treated the same as those with a known mutation, and that will include approaches to safe general anaesthesia.
Significant paralysis in patients with PP Disorders can last for minutes, hours, sometimes days. Prolonged attacks (days to many weeks) with reduced muscle stamina, variable muscle weakness and fatigue, are also a feature and may be frequent. These types of chronic attacks are currently designated as .
Patients may be diagnosed in childhood or adolescence but much evidence shows that diagnosis may be delayed by many decades. Permanent muscle weakness commonly develops over years and may lead in some patients to very significant disability [5].
The triggers for attacks vary according to the form of Periodic Paralysis, and also between individuals with the same PP Disorder, but typical provocations include changes in plasma potassium or glucose levels, exercise, rest after exercise, alcohol, a wide variety of drugs, physiological or psychological stress, inter-current illness, and exposure to cold temperatures.
Adverse reactions to anaesthesia have been reported anecdotally by many patients with a Periodic Paralysis Disorder. It is obviously unknown how many more events may not have been reported or even thought at the time to have been related to the patient’s PPD. Reactions have included difficulty breathing (even clinical respiratory distress), extreme myotonia, spasms of the jaw and other muscles, and prolonged postoperative paralysis. In some cases reported by patients’ families [6], death due to respiratory failure following anaesthesia has occurred. Patients with Andersen-Tawil Syndrome are at peri-operative risk also of cardiac events, classically catastrophic ventricular dysrythmias including torsades de pointes.
Adverse reactions to anaesthesia, including life-threatening events, thus remain a serious concern for patients with Periodic Paralysis Disorders. Recent research has been helpful in defining these reactions, their mechanisms, and how to avoid them.
Because of the rarity of the periodic paralyses, particularly HyperPP and Andersen-Tawil Syndrome, it is not surprising that the published body of good practice in anaesthesia in patients with PPDs is sparse. The practical guidelines in this review are therefore necessarily largely based on sensible practice more than on published experience. No evidence has been found of controlled trials of anaesthetic techniques in patients with PP Disorders (as might be expected given their rarity).
Simple strategies such as good communication and co-operation (between doctors and between doctor and patient), a written Individual Care Plan [7] prepared with the patient and distributed to all relevant staff, close monitoring of muscle function and of glucose and potassium levels, and also cardiac surveillance (especially in ATS), are recommended as the principal measures required to minimize adverse reactions to anaesthesia. Experience of peri-operative management in the PP Disorders, including specific anaesthetic regimes, is outlined as part of a selected literature review, and practical management guidelines are described. (see Part 1 – A Review of the Literature).
Elective (non-emergency) surgery in patients with Periodic Paralysis Disorders
Definitions
For the purposes of these guidelines:
1. The term <surgery> is used to describe any medical or surgical intervention where the patient may need, or will definitely need, any form of anaesthesia or significant sedation (other than minimal local anaesthesia – guidelines for which are outlined by Cheng [56]), thus including procedures such as dental surgery, colonoscopy, cardiac catheterisation, childbirth, & etc.
2. The term <peri-operative> is used here to describe the entire hospital stay for the procedure. Periods of higher risk are obviously actually during the surgery and anaesthetic, but inappropriate management pre-operatively or during post-operative recovery will also increase the risk for patients with PP Disorders.
3. The term <plasma potassium> is used in this review to describe potassium assay in the supernatant fluid of centrifuged blood. Potassium can be measured in both serum and plasma, and the terms are often somewhat inappropriately used interchangeably, but plasma concentrations are 0.1–0.7 mmol/L lower than those in serum [57] However, the clinical significance of this may not be relevant, even in patients with potassium-sensitive PP Disorders
4. The abbreviation <HypoPP> applies to hypokalaemic periodic paralysis types 1, 2 and 3, and to HypoPP associated with Andersen-Tawil syndrome.
General points
1. Genetic Periodic Paralysis Disorders are rare conditions. Evidence-based anaesthetic management is sparse but what evidence there is suggests that safe general anaesthesia can usefully be based on detailed planning, very close communication and co-operation between all relevant healthcare professionals (and with the patient) and the application of general principles of peri-operative care including detailed biometric monitoring. Immediate access to pharmaceutical expertise is important.
2. Many patients with Periodic Paralysis Disorders know a great deal about their conditions – both theoretically from reading the medical literature but also from managing their own conditions, often throughout many decades. Most PP patients do not expect new doctors they see to know anything at all about these rare conditions. Some web-based information about Periodic Paralysis
Disorders that doctors may access can perhaps be inappropriately dogmatic, and sometimes it is just clearly inaccurate, thus many patients find it helpful if doctors are willing to be informed about the patient’s PP Disorder and its management by actually asking the patient. The next most helpful source of appropriate information is likely to be the patient’s principal PP physician.
In a peri-operative context, this situation is succinctly confirmed by Weber and Lehmann-Horn. [58]
- Periodic paralyses are rare diseases
- Physicians are often not familiar with PP
- Patients should be better informed than their doctors
- Anesthesiologists are specialists for anaesthesia, not for rare diseases
3. Many people with PP Disorders have developed over time a very finely balanced use of medication, often a complicated regime of prescribed drugs and over-the-counter medicines and supplements, that they find suit them and keep them as well as possible. The normal hospital practice is to take all home medicines from patients on admission and have some (occasionally all) of them re-dispensed by the hospital pharmacy under prescriptions from hospital doctors (often the most junior members of the team), and finally re-administered by the nursing staff. People with PP Disorders describe a number of problems with this approach including delayed doses, altered dosages, different drug formulations, and doctors who withhold certain drugs or supplements as they are sceptical (or ignorant) about their benefit. If a patient is well enough during a hospital admission to take medication responsibly, and if none of their home medications are newly contraindicated by their clinical condition or by new essential drugs they are being given, then it is ideal for patients with PP Disorders to be allowed if they wish, and when feasible, to self-medicate with their usual regime while in hospital, if necessary with the help of their principal home carer.
4. Some patients with PP Disorders have a detailed understanding of their personal <safe> and <ideal> plasma potassium levels, that will help prevent, or treat, muscle paralysis (and cardiac rhythm crises in ATS). When known, this information should be written in the treatment plan and doctors and nursing staff should pay close attention to it.
5. The pattern of paralysis varies between disorders, between patients, and sometimes in the same patient at different times. Contrary to some web-based information, many patients have acute paralysis in, say, legs only, or an arm, & etc. Tetraplegia, paraplegia or symmetrical paralysis are not diagnostic pre-requisites for acute paralytic attacks in patients with PP Disorders.
Pre-admission: Doctors and other healthcare staff
1. Is this surgical intervention really necessary? Are there any alternative management approaches that could be effective but will avoid anaesthesia?
2. Close co-operation and good communication between all the patient’s relevant doctors is vital for safe planning of the surgical procedure.
3. The main risks in PP Disorders, particularly ATS, are with general anaesthesia. All avenues of anaesthetic alternatives (e.g. regional blocks, intravenous sedation etc) should be explored before a GA is confirmed as necessary. There are a number of reports of alternatives to GA being successfully used in the PP Disorders even for what may be considered as <major> surgery.
4. Despite the exigencies of duty rotas and other administrative considerations it is recommended that the anaesthetist for the procedure is identified, by name, early on in the planning and booking of the surgical intervention. Variants of <We’ll just check who the duty anaesthetist is once we get to Theatre> is unsafe practice for these high-risk patients.
5. Given the risks of anaesthesia (particularly cardiac risks in ATS) it is recommended that an experienced anaesthetist is responsible for the anaesthesia and ideally it will be this anaesthetist who carries out the pre-operative anaesthetic assessment
6. It is recommended that a named doctor (to be appointed by the surgeon if they do not take that role themselves) is responsible for preparing a multi-professional written action plan, an Individual Care Plan. This plan should be discussed with the patient and with the patient’s principal PP doctor before it is finalised and before the patient is admitted to hospital for an elective procedure.
7. It is recommended that all surgery (and sedation-requiring medical interventions) in patients with Periodic Paralysis Disorders is performed only in a hospital setting (and not in Dental Surgeries, Doctors’ Offices, clinics, family doctor premises, or similar unsupported sites), and never on a day-case basis. Full resuscitation facilities should be available in Theatre, and a Critical Care (or equivalent) bed must be available post-operatively. This is particularly relevant for patients with ATS with their peri-operative risks of significant cardiac arrhythmias.
8. Weber and Lehmann-Horn [58] recommend that pre-operative assessment in the PPDs should include: full neurological exam, ECG, chest X-ray, echocardiogram, pulmonary function tests, arterial blood gas analysis and plasma sodium, potassium, calcium, chloride, magnesium, creatine kinase and myoglobin.
9. To avoid provoking paralytic attacks (and acute dysrhythmias in ATS) the patient should be asked about the specific triggers for their attacks – many people with PP Disorders know them well. This information should form part of the Individual Treatment Plan for each patient.
10. Many, particularly older, patients with PP Disorders have some degree of permanent muscle weakness, in some patients it is severe. It is therefore recommended that a physical therapist (physiotherapist) is involved in the pre-operative assessment (focusing on muscular strength and capability, also respiration) so that post-op mobilisation can be planned effectively. Prolonged immobility (e.g. enforced bed rest after surgery) is known to be a potent trigger for many people with PP Disorders
11. There is anecdotal evidence that some people with PP Disorders are particularly sensitive (dosage, side-effects, immune responses) to a wide variety of drugs. A detailed <drug reaction> history should be recorded and taken notice of.
12. Patients with Andersen-Tawil Syndrome are likely to require assessment by their specialist cardiologist before elective surgery. Depending on the surgical and anaesthetic risk, the cardiologist may decide that further investigations are necessary as part of a pre-operative work up
13. Some patients with ATS have significant oro-facial and/or dental anomalies. Specialist oro-pharygeal assessment may be needed as part of pre-op assessment to identify any anatomical features that might make anaesthetic intubation or ventilation more challenging
14. Sleep disorders, including sleep apnoea (SA), are thought to be common in patients with PPDs. Ideally a patient with a PPD will long since have been screened for sleep apnoea, but if not, it is recommended to enquire about symptoms suggestive of SA at the pre-op anaesthetic assessment (symptoms may be subtle and not just <snoring> or <falling asleep in front of the television>). Given that sleep apnoea itself complicates anaesthesia, if undiagnosed SA is strongly suspected clinically it would be appropriate to delay elective surgery until a diagnostic sleep study can be carried out and CPAP treatment initiated if appropriate .
Pre-admission: Patients
1. Patients with periodic paralysis conditions must notify their surgeon and anaesthetist of their condition as early as possible (e.g. in the first out-patient consultation with the surgeon). Patients should take with them their health dossier containing, at least, copies of all relevant medical letters and tests concerning their PP Disorder, and also information relating to any previous surgery and/or anaesthesia and sedation. If they do not already have copies they will hopefully have time before planned surgery to ask their doctors for copies and/or to make an official request to any hospitals and Emergency departments they have been admitted to for copies of their notes. This process can take weeks or more, depending on the hospital and which country they live in.
2. It is recommended that patients write some brief notes before they see the surgeon, to include information they think the surgeon and anaesthetist need to know – which should include details of any previous surgery, previous anaesthetics, any problems with either, and any family history of adverse events with anaesthesia. [59]
3. Patients could usefully ask their principal PP physician if they might agree to summarising points in this review, that are relevant to them, to supplement the referral letter to the surgeon. Perhaps not unreasonably many doctors often take more notice of a letter from another doctor rather than of a published review.
4. Also ask their PP physician if he/she could keep lines of communication open with the surgeon, and also the anaesthetist if possible.
5. Asymptomatic family members should mention that they have relatives with a form of Periodic Paralysis as milder forms of PP may be asymptomatic and remain undiagnosed. Ideally, family members of a PP patient with a known genetic mutation will have been screened for the same mutation, but this practice is not universal and of course excludes a number of patients with Periodic Paralysis Disorders in whom a known genetic mutation has not been found. Some patients with PP Disorders have been diagnosed only after they have experienced paralysis following anaesthesia. Thus being asymptomatic in an affected kindred may mean an individual actually has a mild version of PP and is therefore at risk during anaesthesia. Not all PP patients have a positive family history – it is thought that even up to 30% of cases involve sporadic genetic mutation.
6. During the appointments with the surgeon and anaesthetist it is important that the patient discusses their usual medication regime and asks, if they wish, to be responsible for their own routine medications while in hospital (see above).
Admission to hospital: patients
1. Patients might wish to take copies of this article with them into hospital and give them to anyone that they think needs to read it to help look after them safely .
2. Patients should provide contact details of their principal PP physician (and with Andersen-Tawil, their cardiologist) so that the surgeon and anaesthetist can obtain information and advice when necessary. This should include details of 24-hour availability of expert advice, or, if such cover is not available from their usual physicians, from a State, or National, Periodic Paralysis centre even if they are not actually under their care.
3. It is recommended that patients take in enough of their normal medications and supplements to last for at least double their expected duration of stay and resist handing them over to the nursing staff until they have discussed their medication with the ward doctor, including the possibility of self-medication while in hospital, if wished (see above).
4. If a patient with PPD is being treated for sleep apnoea with CPAP at home, it is recommended that:
a. they take in their machine and all its attachments – mask, hose, leads etc (and an extension electrical lead in case there is no available socket immediately beside their bed). All should be clearly labelled with the patient’s name.
b. Post-operatively, once the patient has been extubated and is breathing spontaneously, it may be helpful if they are then given their own CPAP machine and mask to use in the Recovery suite. This should be discussed at the pre-operative anaesthetic assessment; on the day it will be the anaesthetist’s decision of course.
c. Oxygen supplementation can be branched to CPAP machines [60], the flow rate will depend on the machine and its mode setting.
d. If a patient’s sleep apnoea is position-dependent (for example, as is common, much worse when they are lying flat on their back) then they should tell the anaesthetist about that at their assessment and ask (if the type of surgery allows) if they might be placed in another position
(e.g. lying on their side, or head of the bed elevated) until they are fully recovered from the anaesthetic and breathing normally.
e. To optimise respiratory function and general recovery it is recommended that PP Disorder patients with sleep apnoea use their CPAP machine all night and every night while in hospital and also during the daytime when they are dozing.
f. If the surgical site is <head and neck> then expert advice may be needed to enable the use of CPAP post-operatively. This may be obtained from a specialist respiratory team at the hospital and/or from the patient’s usual CPAP technician (access to CPAP technicians while in hospital will vary between units and between countries).
Peri-operative management: Overriding principles
1. Wide distribution to relevant staff of the written Individual Care Plan for the patient, which will have been prepared in consultation with the patient and with their principal PP physician
2. Multi-disciplinary teamwork, involving multiple medical specialities and multiple healthcare professions.
3. Avoid triggering paralytic attacks, avoid changes in the plasma potassium level that are unsafe in that patient and, in Andersen-Tawil syndrome particularly, avoid triggers – generic and specific – of acute cardiac dysrhythmias.
4. Too much monitoring of neuromuscular status, plasma electrolytes and glucose, acid-base balance, continuous ECG cardiac surveillance, etc, is very unlikely ever to be a problem. Too little monitoring may well be regretted
5. Post-operative care should be in a high-dependency unit for at least 24-48 hours, or until the patient is clinically stable, has normal muscular strength for them, and is maintaining a stable plasma potassium level within that patient’s ideal steady-state range (or, if the individual’s ideal range is not known, then within the laboratory normal range)
6. Staff should take notice of the patient and their principal home carers if they say that <concerning the Periodic Paralysis Disorder – things are not going well>. Clinical expertise amongst patients and their home carers is common in the PP Disorders
7. Be prepared for the worst e.g. Resuscitation facilities (Crash Cart) available in Theatre and the Recovery Suite; post-operative admission to a high-dependency Unit & etc.
8. But anticipate the best – there are many precedents, anecdotal and published, of successful and uneventful regional and general anaesthesia in patients with Periodic Paralysis Disorders
Peri-operative management: general points
1. Unexpected post-operative paralysis in a patient with PP may not be a prolonged response to the anaesthetic or sedation but instead may well be a PP attack. Urgent medical assessment is vital and if the patient is unconscious or cannot speak it should include assessment and advice from the patient’s principal home carer who is likely to have extensive experience of the patient’s paralytic attacks so can offer information which will be useful to the doctors in their differential diagnosis of a paralysed state.
2. Bear in mind that some patients have only been diagnosed for the first time as having a Periodic Paralysis Disorder because of their abnormal responses to anaesthesia and surgery. Unexpected peri-operative cardiac arrhythmias, muscular pareses or paralysis, or acutely abnormal plasma potassium levels, should alert doctors to this possibility.
3. There is a rarely reported association of Malignant Hyperthermia Syndrome in Periodic Paralysis Disorders. The risk remains poorly defined but the anaesthetist should be aware of this, and be prepared for it.
4. Ideally employ neuromuscular monitoring throughout the intervention
Peri-operative management: Classical triggers and their management:
Applicable to all patients with a Periodic Paralysis Disorder
Maintain appropriate body temperature – in most patients this means warm.
There are a few anecdotal reports of patients who have attacks triggered by excessive heat and this should be noted in their Individual Treatment Plan, but the majority of patients with PP Disorders report worsening of symptoms and attack triggering with cold temperatures and this is a major peri-operative risk. Many patients with HyperPP also have some variant of cold-aggravated myotonia. Many hospitals have brutal air-conditioning and patients are often only given one thin blanket and a (often much too small) thin cotton gown. Theatre Suites are usually kept very cool and hypothermia during surgery will be compounded by body exposure and the peripheral vasodilatation that occurs with general and regional anaesthesia.
Thus – keep the patient warm by, for example, increasing the bedroom temperature, generous bed clothes, and during surgery by increasing the room temperature in Theatre, using warmed solutions intravenously and also when bathing the operative site. A variety of other methods are effective. Useful resources are the Cochrane Systematic Review [62] and NICE Guidance [63].
Attacks triggered by muscular exertion and during rest after exercise
This should not be relevant in an in-patient situation. Patients should keep within the limits of their routine exercise regime in the days before admission – the wise patient will not have undergone strenuous physical activity just before planned surgery.
Avoid prolonged immobility
1. A pre-op physical therapy assessment is important
2. When the patient is confined to bed, encourage as much limb movement as possible to prevent muscular weakness (and to prevent venous thrombosis)
3. When feasible arrange for periodic breaks from electronic monitoring (or other items that inhibit mobilisation) to enable the patient to move around
4. Full post-operative mobilisation, with physiotherapy supervision as necessary, as soon as clinically possible
5. The patient should be given an Individual Discharge Plan that includes a description of appropriate physical exercises (relevant to the type of surgery) that they should continue at home until surgical healing has occurred.
Prevent (and treat promptly when necessary) fatigue, stress, pain and anxiety
All of these are known to be triggers in the PPDs, particularly adrenergic stress with its cardiac manifestations (especially to be avoided in ATS) and metabolic effects (hyperglycaemia, hypokalaemia).
1. Give anxiolytic, analgesic and/or sedative medication as necessary BUT be aware that some patients with PPD report triggering of paralysis with various sedative drugs. This information should be recorded in the Individual Treatment Plan.
2. Minimise waking up the patient for routine nursing observations. A balance should be sought between safe observation levels and allowing the patient to have daytime rest and a decent night’s sleep, so reducing fatigue. For example it seems unnecessary to wake a patient up to record their manually measured pulse and blood pressure when that is being recorded anyway if they are connected to continuous cardiac monitoring.
Avoid dehydration
This has been anecdotally reported as an attack trigger in each of the PP Disorders.
Great care with medications.
There are many anecdotal reports, in a number of patients with each of the PP disorders, of idiosyncratic triggering of attacks by specific drugs. It is very important that this information is elicited from the patient and written down in the Individual
Treatment Plan. There is a long list of anecdotal culprit drugs, including novocaine, anti-histamines, epinephrine, benzodiazepines and statins.
Avoid any other trigger particular to the individual. There are also anecdotal reports of triggering of attacks by, for example, fluorescent lighting, very noisy environments, food colourings, and monosodium glutamate. Such <particular> triggers should be recorded in the Individual Treatment Plan and avoided during that patient’s admission.
Hypokalaemic periodic paralysis
Avoid hypokalaemia – low plasma potassium (relative or absolute)
1. The personal experience of many patients with HypoPP contradicts the often-published <rule> that paralysis will only occur in them when the plasma potassium is less than 3.0 mmol/l. Patients often report having paralytic attacks with a plasma potassium still within the laboratory normal range or just below it. It might well be that it is the sudden shift in potassium from their usual level that is the significant feature, not the actual numerical end-result of the plasma level. To date there is inadequate published data to confirm or refute this.
2. Frequent monitoring of the plasma potassium before, during, and after surgery. Empirically, depending on assay results and clinical condition, even half-hourly for 6-12 hours peri-operatively.
3. Potassium supplementation: maintain levels at high-normal i.e. 4.5 to 5.0 mmol/l, possibly higher if the patient or their PP physician knows from experience that is necessary in the individual, possibly lower if the patient is one of the rare people with HypoPP, or ATS with HypoPP, who report that their symptoms may also be triggered by a relatively high plasma potassium.
4. While <nil by mouth>, supplement potassium intravenously as necessary (normal protocol), change to oral replacement as soon as possible
5. For oral supplementation in the immediate peri-operative period, immediate-release potassium preparations are more appropriate than slow-release formulations.
6. Guidance on IV and oral potassium supplementation can be obtained from the hospital pharmacy. Confusion between <milligrammes (mg)>, <millimoles (mmol)>, and <milliequivalents (MEq)> of potassium is not uncommon, and the equivalence varies with the particular potassium salt used. A very useful resource is Levitt’s review [64].
7. All patients should restart their usual prophylactic treatment after surgery as soon as they can take oral medication.
8. Note that some patients with HypoPP (and ATS with HypoPP) require very large doses of prophylactic potassium.
More than 100 MEq (equivalent to more than 7.5 G of potassium chloride) per day is not uncommon. This level of dosing can be rather startling to healthcare staff (and pharmacies) who have not met the patient before, so it is important that the patient’s prophylactic regime is clearly annotated in their Individual Treatment Plan and that they can return to their full-dose prophylaxis as soon as possible post-operatively.
9. Take care with intravenous potassium replacement to avoid a <rebound hyperkalaemia>. There is no <total body lack> of potassium in HypoPP – instead the potassium becomes trapped in skeletal muscle (and the myocardial cells in ATS). Thus when the paralytic attack recovers, potassium is released back into the intravascular space and ensuing hyperkalaemia is theoretically a real risk. Frequent plasma assay and continuous ECG monitoring should be continued for at least 12 hours after intravenous potassium supplementation has stopped and/or the paralysis or dysrhythmia has resolved. However, as far as is known this rebound hyperkalaemia in the PP Disorders has only been reported once with IV supplementation (Patangi et al [21]) and no published reports have been found of it happening during oral supplementation. Anecdotally it is thought to be extremely rare and in the context of normal renal function would be likely to be brief. It would be more of a concern in the elderly and those patients who are also taking potassium-sparing drugs and/or who have reduced kidney function.
10. Avoid if possible all drugs that provoke potassium loss [65] for example many diuretics and oral or systemic corticosteroids. If these drugs are vital then increase the frequency of plasma potassium surveillance.
11. Treat promptly any potassium-losing states such as diarrhoea or vomiting
Avoid hyperglycaemia – high blood glucose (relative or absolute)
Carbohydrate sensitivity (particularly to simple sugars – oral complex carbohydrates may sometimes be tolerated) varies between patients with HypoPP but in many people it is very significant. There is some evidence (Yoon et al [27]) that ATS patients with HypoPP may be less sensitive to carbohydrate loads than people with <classical> HypoPP
1. Do not give oral glucose or use intravenous glucose solutions
2. To avoid triggering attacks, many patients with HypoPP have to follow a very strict dietary regime at home and it is very important that this is maintained while in hospital. A routine <diabetic diet> is rarely suitable without significant modifications and many patients with each of the PP Disorders find that frequent small meals suit them much better than two or three large ones each day. The patient’s personal dietary regime should be included in the Individual Treatment Plan. A senior nurse should be personally responsible for communicating this to the kitchens, and for ensuring the suitability of the food and drink actually given to the patient and for the appropriate intervals between meals. This should not be delegated to the ward’s domestic staff. When feasible in the circumstances, the patient’s family and friends could also bring in appropriate food and drinks.
3. Despite it being superficially counterintuitive, some HypoPP patients also report missing meals or fasting as triggers of their attacks (thought to be caused by liver release of glycogen in fasting states thus provoking insulin release with potassium being driven into the muscles). This should be avoided.
4. A light low-carbohydrate meal the night before surgery is often ideal
5. Frequent monitoring of peri-operative blood glucose, and control of any hyperglycaemia. But –
6. Beware over-enthusiastic correction of hyperglycaemia, especially in Andersen-Tawil with HypoPP. Hypoglycaemia has been shown to increase ventricular and atrial ectopy [66] – often precursors of significant abnormal heart rhythms.
Avoid saline loading – intravenous solutions and/or high dietary intake
1. Salt sensitivity as a trigger is variable between patients but in many people it is very significant
2. Do not use IV saline infusions. Suitable alternatives are Ringers or Hartmann’s, with potassium added to the solution as required (see Table 2)
Hyperkalaemic periodic paralysis
Avoid hypERkalaemia – high plasma potassium (relative or absolute)
1. Maintain potassium at that patient’s safe levels if known; if not known, maintain at a low-normal level
2. Avoid oral potassium loads (appropriate food and drink while in hospital)
3. Avoid the routine potassium supplementation of IV infusion fluids
4. Avoid (or take great care in) prescribing medications that raise the plasma potassium e.g. ACE-inhibitors, angiotensin receptor blockers, aldosterone antagonists
5. During the routine storage of whole blood for transfusion, the supernatant plasma potassium level increases over time. Rare cases of transfusion-induced hyperkalaemia have been reported (none of the patients were mentioned as having a PP Disorder). If a patient with HyperPP is anticipated to require significant quantities of peri-operative transfused blood, particularly on the rare occasions that <whole blood> will be required, it is recommended that this is discussed with the Transfusion department at least a week prior to surgery.
Avoid hypoglycaemia – low blood sugar levels (relative or absolute)
1. Avoid fasting the patient before surgery when possible or give pre-surgery glucose when fasting
2. Use IV glucose infusions with regular checks of blood glucose. Maintain normal levels with appropriate IV fluids or oral simple carbohydrates
Andersen-Tawil Syndrome
The cardiac polarisation abnormalities in ATS may not be clinically overt in steady state in all patients – thus patients previously assumed to have <classic> HypoPP or HyperPP (but never genetically tested, or tested but found to be negative for the common mutations) may in fact actually have ATS and may present with ATS-like cardiac events for the first time during times of risk, such as during surgery and anaesthesia. (On retrospective reading the patient in Rooney’s 1988 case study might possibly have had ATS as he had ECG evidence of bigeminy as well as having periodic paralysis. The paper does not mention his genetic status) Packer and Strätling [35] succinctly summarise the drug challenges in patients with ATS: <The long list of relative or absolute drug contra-indications include many commonly used emergency drugs: adrenaline, phenylephrine, ephedrine, metaraminol, atropine, glycopyrolate, neostigmine, amiodarone, other Class I and III compounds, cocaine, other local anaesthetics if used in large volumes, suxamethonium, non-depolarising muscle relaxants, volatile anaesthetics, thiopentone, ketamine, antihistamines, bronchodilators, ondansetron, dexamethasone, prochlorperazine, and others…>.
Avoid triggering paralysis attacks: triggers for muscle paralysis in patients with ATS will depend on whether they have associated Hypokalaemic PP or (more rarely) hyperkalaemic or normokalaemic PP. Thus, management guidelines as above, depending on the type of potassium sensitivity. Even rarer still, but there are anecdotal reports, some patients with ATS need to keep their potassium within a very tight range (and not higher or lower) to avoid paralysis or acute dysrhythmias.
Prevention and management of acute cardiac dysrythmias
The safe cardiac management of perioperative patients with Andersen-Tawil Syndrome is complex and requires the very close co-operation of an expert anaesthetist and an expert cardiologist. When patients with Andersen-Tawil undergo surgery it is recommended that the peri-operative availability (within just a few minutes, and in person) of the patient’s cardiologist is confirmed once the surgery is booked – even, for major surgery under GA, the anaesthetist should consider asking the cardiologist to actually be present in Theatre and in Recovery throughout the immediate peri-operative period. If the patient’s usual cardiologist cannot be available on the day then a fully briefed substitute senior cardiologist should be appointed and confirmed before the patient’s admission to hospital. The detailed cardiac management of ATS in the peri-operative period is outside the scope of this review. A brief summary of published recommendations includes:
1. All drugs which prolong the QT interval are contra-indicated, whether or not the patient has a permanently prolonged QTc interval.
A continually updated web-based list of such drugs is available at www.crediblemeds.org.
2. Avoid sympathetic stimulation – continue, or prescribe de novo, peri-operative beta blockade, also appropriate anxiolysis and analgesia
3. Strict care with manoeuvres or medication to avoid bradycardia (which has long been recognised to effect cardiac repolarisation and thus increase the risk of significant dysrhythmias)
4. Strict monitoring, and supplementation when necessary, of potassium levels
5. Magnesium and calcium supplementation are likely to be beneficial even when serum assay is within normal limits
6. Some patients with ATS have an implantable defibrillator – guidelines on the perioperative management of patients with ICDs are available [67].
7. Continuous ECG monitoring until the patient is ready to be normally mobile for them, has a stable ECG, and stable and acceptable plasma potassium levels
The Potassium Aggravated Myotonias
Specialist peer-reviewed guidelines for anaesthesia in paramyotonia congenita and potassium aggravated myotonias appear to be sparse but in a case report of a patient with PMC, Kang et al [68] usefully review the literature and describe recommendations for management that include:
1. Avoid depolarising muscle relaxants and anticholinesterases
2. Propofol might be the agent of choice within the volatile anaesthetics
3. Epidural anaesthesia may have benefits over general anaesthesia
4. Avoid exposure to cold
5. Careful monitoring of electrolytes, particularly potassium, is important
6. Calcium gluconate should be available at all times to treat acute hyperkalaemia or myotonic stiffness
Anecdotal evidence includes:
1. Be alert for extended periods of leg weakness, with the risk of falls, after epidural anaesthesia
2. Liquid calcium gluconate syrup supplements have helped with post-epidural muscle weakness and cramping. Calcium given during the myotonic stiffness can prevent or lessen a full attack
PRACTICAL MEASURES – Emergency surgery
1. It is recommended that patients with Periodic Paralysis Disorders who require emergency general or regional anaesthesia, and/or significant sedation, are immediately transferred to a hospital with specialist anaesthetic facilities and a high dependency unit.
2. Then, apply as many of the above guidelines that are feasible under the circumstances
(END)
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List of References for Parts 1 and 2 of ‘Anaesthesia and peri-operative care in the primary Periodic Paralysis Disorders’
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Anaesthesia and peri-operative care in the primary Periodic Paralysis Disorders.
PART 2: Practical Guidelines
Baughan ASJ, Cavel-Greant D, Megalo J and Weber F.
Published April 2016 at <www.hkpp.org> Comments are welcome.
This web edition will be updated as necessary.