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Published on 8 May 2017

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Postoperative management of neurological drug therapy

This article concentrates on the postoperative drug management of epilepsy, Parkinson’s disease, and myasthenia gravis: three conditions in which medicines play a critical role in their management

 

Ben Dorward DPharm MRPharmS
Lead Neurosciences Pharmacist, Sheffield Teaching Hospitals NHS Foundation Trust, UK

 

This article concentrates on the postoperative drug management of epilepsy, Parkinson’s disease, and myasthenia gravis: three conditions in which medicines play a critical role in their management

 

Ben Dorward DPharm MRPharmS
Lead Neurosciences Pharmacist, Sheffield Teaching Hospitals NHS Foundation Trust, UK

 

Neurological diagnoses are remarkably common but encompass a wide array of often-rare conditions. Drug therapy is indicated for many neurological conditions, which may be off-licence or unlicensed.

The clinical pharmacy team has a pivotal role to play in minimising and mitigating for potential disruption to the routine drug management brought about by surgery. The initial admission to hospital is identified as one of the highest risk periods for prescribing errors generally;1 for critical medicines, such as those indicated for these conditions, the risks to patients from omission and errors are amplified, and may hinder recovery from surgery. Several studies of patients with Parkinson’s disease admitted to hospital have demonstrated unacceptably high rates of medication error2,3 and drug dose omissions.4

The principles to approach
Established treatments should be continued where possible and pre-emptive planning is always preferable, with involvement of the neurology team if necessary and, where available, specialist nurses and pharmacists. Where indicated, insertion of a nasogastric feeding tube can ensure that routine oral therapy can continue to be administered and the pharmacy team can advise on drug administration via this route, particularly if there is a requirement to swap from slow-release formulations.

Each patient must be treated individually and many will have very specific drug regimes. For example, dopaminergic drug therapies for Parkinson’s disease and anticholinesterase drugs for MG (pyridostigmine and neostigmine) may need to be given frequently, and at very specific times, for optimal symptom control.

Pharmacist-led research exploring patients with Parkinson’s disease admitted to hospital identified anxiety as a central theme to their experiences.5 Where feasible and appropriate, medication self-administration can help patients to keep control of their condition. It is imperative that patients and their carers are involved in any necessary therapeutic alterations.

The importance of ascertaining an accurate drug history, and ensuring prescribed medicines are available and administered, cannot be overstated. The fluctuant and progressive nature of these conditions, and the pharmacological properties of the drug treatments, can necessitate frequent drug alterations and dose titrations, such that primary care records may not accurately reflect the current regime. Where possible, the patient and/or their carer must be consulted to verify the drug history; recent neurology clinic letters and clinical specialist nurses can also be useful resources for further verification. Furthermore, the involvement of a specialist nurse, who has often built a supportive relationship with patients and their carers over the course of their condition, can provide invaluable psychological reassurance during the admission.

Epilepsy
Epilepsy is a heterogeneous seizure disorder presenting uniquely different challenges and issues to affected individuals. Anti-epileptic drugs (AEDs) do not cure epilepsy but control the recurrence of further epileptic seizures in up to 70% of cases.6 Postoperatively, AEDs should be continued wherever possible because abrupt withdrawal poses the risk of rebound seizures and even status epilepticus. When enteral administration is not possible or absorption may be impaired, a number of AEDs are available in parenteral formulations to enable continuation (see Table 1).

 

 

When an AED is unavailable in parenteral form it is advisable to discuss with the neurology team if an alterative AED should be initiated. The paucity of evidence, heterogeneity of epilepsy, and the requirement to usually slowly titrate AEDs, present challenges in how to manage situations when established AEDs cannot be continued. An AED with broad seizure type efficacy that can be loaded to rapidly attain therapeutic levels is ideal. Phenytoin and valproate exhibit such properties although their use is not without issue. Intravenous phenytoin requires monitoring for potential cardiotoxicity and is an irritant, although the latter risk can be reduced by using fosphenytoin.

 

Levetiracetam is increasingly used for the acute control of seizures by initiation with loading doses followed by sometimes higher than usual maintenance doses.7 Although this practice is currently off-licence and the evidence to support it is of variable quality, clinical experience does support that levetiracetam is well tolerated and a robust randomised study is currently in progress assessing its relative efficacy in the management of status epilepticus.8

Certain drug groups can potentially lower the seizure threshold, warranting cautious or avoidance of use in epilepsy. Opioids have been implicated with causing seizures but are used in people with epilepsy (although tramadol should be avoided if possible or used with extreme caution). Nefopam is contra-indicated in the UK in convulsive disorders and should be avoided. The phenothiazine anti-emetic prochlorperazine can lower the seizure threshold, as can the quinolone antibiotics, and they should be avoided if possible.

A significant pharmacokinetic interaction can occur between carbapenems and valproate, with the former able to produce a rapid and profound reduction in levels of the latter.9 The mechanism of this interaction is not fully elucidated and valproate levels are not always restored by dose increases and loading doses. When such a combination is unavoidable, pre-emptively monitoring baseline and subsequent daily valproate levels can detect the occurrence and magnitude of the interaction, but the neurology team should be consulted on how to manage the individual patient.

 

Parkinson’s disease
The mainstay of treatment for idiopathic Parkinson’s disease is dopaminergic therapy in the form of levodopa (L-DOPA) products and dopamine agonists, or monoamine oxidase B inhibitors (MAO-BI). Patients may also have undergone surgical interventions, such as deep brain stimulation.

Abrupt withdrawal of L-DOPA, and sometimes dopamine agonists, can result in a serious and potentially fatal syndrome of muscle rigidity, with other features such as pyrexia and confusion that clinically resemble neuroleptic malignant syndrome. A dopamine agonist withdrawal syndrome has also been described with features that include anxiety, panic attacks, dysphoria, and generalised pain.10 MAO-BIs, such as rasagiline, have potential to complicate anaesthetic management and most sources believe it reasonable to withhold them for surgery if acceptable to the patient.11

When enteral drug administration is not possible, the parenteral dopamine agonists, rotigotine and apomorphine, can be used. Rotigotine patches are easier to use than subcutaneous apomorphine and do not require pre-treatment with domperidone. It would be advisable to consult a specialist Parkinson’s team if considering the use of apomorphine. Dose conversion recommendations between Parkinson’s drugs and rotigotine have been published.12 It is important to consider these are guides and it may be necessary to alter the dose according to the response, which should be assessed daily. More cautious dosing is advised if confusion or delirium is present.

To control postoperative nausea and vomiting, centrally acting dopamine antagonists such as metoclopramide, prochlorperazine and droperidol must be avoided because they can acutely exacerbate motor symptoms. Domperidone is a peripherally acting dopamine antagonist and suitable for people with Parkinson’s disease.

Cyclizine can also be used, as can serotonin 5-HT3 antagonists such as ondansetron, although this should be avoided in combination with apomorphine as profound hypotension can be induced.

MG
MG is an autoimmune neuromuscular disorder characterised by fatigable weakness of skeletal muscle. MG ranges from purely ocular symptoms, to generalised weakness that can progress, sometimes rapidly, to myasthenic crisis where diaphragmatic and intercostal weakness results in respiratory failure. Consequently there should always be a low threshold for anaesthetic and neurology involvement.

Symptomatically, MG is managed by anticholinesterase drugs but immunosuppressive treatment is often required to address the underlying autoimmune pathology. Steroids are the first-line immunosuppressive therapy and the history of steroid exposure should be verified to identify the potential for hypothalamic–pituitary axis suppression and the need for perioperative supplementation. Azathioprine and mycophenolate are commonly used as steroid-sparing agents to control MG. Their effects on the immune system are such that short-term omission of a few doses is unlikely to be detrimental.

Surgery is a potential precipitant of myasthenic crisis. In patients with coexisting thymoma, thymectomy is a treatment option for MG, and a recent trial has shown improved outcomes.13 Ideally surgery should be undertaken when MG is well controlled.14 For elective procedures, intravenous immunoglobulin (IVIg), which produces a rapid but relatively short-lived immunomodulatory effect, can be given pre-operatively. Plasma exchange is also an option if IVIg is contra-indicated.

Electrolytes should be closely monitored, particularly potassium and phosphate, and deficiencies promptly corrected to optimise muscle function. Magnesium is known to interfere with neuromuscular transmission and IV infusions have been associated with inducing myasthenic crisis. Therefore, if indicated, the correction of hypomagnesaemia needs to be undertaken slowly and cautiously, avoiding IV administration if possible and certainly at rapid infusion rates.

Anticholinesterases used for symptomatic control of MG should continue postoperatively. When enteral administration is not possible, parenteral neostigmine can be given. There are no direct comparable studies but 60mg pyridostigmine is approximately equivalent to 0.5mg IV neostigmine, or 1–1.5mg by subcutaneous or intramuscular administration,15 which are the preferable routes that result in less fluctuant effects. Neostigmine is shorter-acting and may need to be given more frequently based on the patient response, which must be closely monitored.

 

 

A number of drugs are associated with unmasking or exacerbating myasthenic symptoms, or experimentally, have been shown to alter neuromuscular transmission; the risk is highest with aminoglycosides and telithromycin (see Figure 1). These drugs should be avoided if possible but if there is no feasible alternative the indication for the drug, such as an untreated infection that can exacerbate MG, may outweigh the risk and treatment may become necessary with the caveat of closely monitoring the patient. Well-controlled MG will be more resilient to the potential effects of these drugs.

 

Key points

  • Medication to manage Parkinson’s disease, epilepsy and myasthenia gravis (MG) should be continued wherever possible to avoid potentially serious sequelae from their abrupt withdrawal.
  • Some commonly used perioperative medicines can adversely affect control of epilepsy, Parkinson’s disease and MG and should be avoided wherever possible.
  • Pre-emptive planning, with the involvement of neurology teams is best where there is the possibility for interruption to oral absorption (for example, high risk for ileus or postoperative nausea and vomiting).
  • Wherever possible, involve the patient and/or their carers in therapeutic decisions who, as experts in their own condition, can assist in the assessment of any necessary changes made to their therapy.
  • Re-initiate the usual oral drug therapy at the earliest opportunity.

 

References

  1. Dornan T et al. An in depth investigation into causes of prescribing errors by foundation trainees in relation to their medical education – EQUIP study. London: General Medical Council;2009.
  2. Gerlach O et al W. Deterioration of Parkinson’s disease during hospitalization: Survey of 684 patients. BMC Neurology 2012;12:13.
  3. Gerlach O, Broen M, Weber W. Motor outcomes during hospitalization in Parkinson’s disease patients: A prospective study. Parkinsonism Relat Disord 2012;19:737–41.
  4. Derry CP et al. Medication management in people with Parkinson’s disease during surgical admissions. Postgrad Med J 2010;86(1016):334–7.
  5. Dunsmure L, Lucas B, Acomb C. Parkinson’s disease medicines management issues associated with the admission of patients in hospital. Hosp Pharm Eur 2012;63(July/August):60–2.
  6. Perucca P, Tomson T. The pharmacological treatment of epilepsy in adults. Lancet Neurol 2011;10:446–56.
  7. Jones S et al. A protocol for the inhospital management of convulsive status epilepticus in adults. Pract Neurol 2014;14:194–7.
  8. Bleck T et al. The established status epilepticus trail 2013. Epilepsia 2013;54(Suppl 6):89–92.
  9. Spriet I et al. Interaction between valproate and meropenem: A retrospective study. Ann Pharmacother 2007;41:1130–6.
  10. Pondal M. Clinical features of dopamine agonist withdrawal syndrome in a movement disorder clinic. J Neurol Neurosurg Psychiatry 2013;84(2):130–5.
  11. Lieb K, Selim M. Preoperative evaluation of patients with neurological disease. Semin Neurol 2008;28(5):603–10.
  12. Brennan KA, Genever RW. Managing Parkinson’s disease during surgery. BMJ 2010;341:990–3.
  13. Wolfe GI et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med 2016;375(6):511–22.
  14. Sussman J et al. Myasthenia gravis: Association of British Neurologists’ management guidelines. Pract Neurol 2015;15:199–206.
  15. UK Medicines Information. How do you convert an oral pyridostgmine dose to a parenteral neostigmine dose? NHS Evidence; 2012. www.medicinesresources.nhs.uk/upload/NHSE_248.2final.doc (accessed April 2017).


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