Table 1.
Voting results of the final Delphi round per statement
| Question | Mean | % of people voting 4 or 5 | Consensus |
|---|---|---|---|
| General | |||
| We need to update the IMP table of potentially harmful drugs for mitochondrial patients version 3 (https://www.mitopatients.org/mitodisease/potentially‐harmful‐drugs) | 4.87 | 100 | Strong |
| Good clinical practice including general indications, contraindications, clinical monitoring and side effects for all drugs must always kept in mind (with or without mitochondrial genetic defect). They will not be discussed in this consensus | 4.94 | 100 | Strong |
| For all drugs where clear evidence in vivo of mitochondrial toxicity is absent or poor, they can be used with careful monitoring in the first few days of treatment for potential side effects and measurement of blood lactate | 4.19 | 93.7 | Strong |
| There is a great need for further studies to determine a) the criteria for drug mitochondrial toxicity in humans, and b) which specific drugs are toxic for mitochondria and must be avoided | 4.25 | 75 | Strong |
| Analgesics‐Antipyretics‐NSAIDs‐Corticosteroids | |||
| Paracetamol is not contraindicated in primary mitochondrial disease (PMD) | 4.56 | 87.5 | Strong |
| Do you consider that steroids are safe to use in acutely ill patients with PMD? | 4.46 | 100 | Strong |
| It is safe to use steroids in patients with Kearns‐Sayre syndrome | 4.13 | 86.6 | Strong |
| NSAIDs can be safely used in PMD | 4.31 | 87.5 | Strong |
| It is reasonable to avoid NSAIDs for long periods in PMD with renal or hepatic or gastrointestinal involvement | 4.31 | 93.75 | Strong |
| Use of aspirin is safe in PMD | 4.56 | 93.75 | Strong |
| Alcohol | |||
| Alcohol in large amounts (above recommended daily intake) is generally toxic and should be avoided | 4.37 | 93.75 | Strong |
| Alcohol consumption within the limits recommended by national guidelines appears non‐toxic in PMD | 5 | 100 | Strong |
| Anaesthetics | |||
| It is safe to use articaine in PMD | 4.75 | 100 | Strong |
| It is safe to use bupivacaine in PMD | 4.81 | 100 | Strong |
| It is safe to use lidocaine in PMD | 5 | 100 | Strong |
| It is safe to use volatile anaesthetics in PMD | 4.62 | 100 | Strong |
| It is safe to use fentanyl in PMD | 4.75 | 100 | Strong |
| Ketamine is safe in general anaesthesia for patients with PMD | 4.75 | 100 | Strong |
| Barbiturates are safe in general anaesthesia for patients with PMD | 4.56 | 93.75 | Strong |
| Propofol is safe in induction anaesthesia in PMD | 3.81 | 81.25 | Consensus |
| Extra caution and monitoring should be considered for patients with PMD manifesting predominantly with myopathic phenotype when neuromuscular blockade is required for general anaesthesia and surgery | 4.25 | 87.5 | Strong |
| Non depolarizing neuromuscular blocking agents are safe for general anaesthesia in patients with PMD | 4.56 | 100 | Strong |
| Antibiotics | |||
| As a general approach, short term (< 7 days) antibiotic treatment is unlikely to be a problem in PMD. Infection is a much greater risk than short term antibiotics | 4.75 | 100 | Strong |
| If indicated, linezolid could be used in mitochondrial disease, with careful lactate monitoring, particularly in children and other patients with pre‐existent lactic acidaemia | 4.56 | 100 | Strong |
| It is safe to use quinolones in PMD | 4.44 | 100 | Strong |
| Aminoglycosides should be avoided in patients with predisposing mitochondrial DNA mutations (eg, m.1555A > G and m.1494C > T) for ototoxicity | 4.81 | 100 | Strong |
| Topical chloramphenicol use is safe in PMD | 4.62 | 100 | Strong |
| It is safe to use tetracyclines in PMD | 4.75 | 100 | Strong |
| It is safe to use ceftriaxone in PMD | 4.87 | 100 | Strong |
| Antidepressant‐Neuroleptic drugs | |||
| The use of antipsychotics medications when they are clinically indicated is not contraindicated in PMD | 4.19 | 87.5 | Strong |
| Quetiapine can be safely used in PMD despite some studies in rodents or cell lines indicate potential mitochondrial toxicity | 4.31 | 93.75 | Strong |
| Fluphenazine could be safely used in PMD | 4 | 75 | Strong |
| Haloperidol can be safely used in PMD despite some studies in rodents or cell lines indicate potential mitochondrial toxicity | 3.81 | 75 | Consensus |
| It is safe to use tricyclic antidepressants in PMD | 4.87 | 100 | Strong |
| It is safe to use chlorpromazine in PMD | 4.75 | 100 | Strong |
| It is safe to use clozapine in PMD | 4.56 | 100 | Strong |
| It is safe to use risperidone in PMD | 4.56 | 100 | Strong |
| Antidiabetic drugs | |||
| It is safe to use metformin in PMD | 4.56 | 100 | Strong |
| It is safe to use glitazone in PMD | 4.37 | 100 | Strong |
| Antiepileptic drugs | |||
| Since there are no descriptions of toxicity of midazolam or other benzodiazepines (BDZ) in PMD, it is correct to assume that midazolam or other BDZ could be used in acute seizure in PMD, or be used as anaesthetic | 4.56 | 100 | Strong |
| Valproic acid should be avoided only in POLG patients | 4.25 | 81.25 | Strong |
| In non‐POLG patients with mitochondrial disease, without liver disease, valproic acid could be used to manage refractory epilepsy and refractory mood disorders | 4.4 | 100 | Strong |
| Carbamazepine is safe in PMD | 4.12 | 75 | Strong |
| Oxcarbazepine is not contraindicated in PMD | 4.37 | 93.75 | Strong |
| Oral phenobarbital is safe in patients with PMD | 4.6 | 100 | Strong |
| In refractory mitochondrial status epilepticus, barbiturates in appropriate settings could be used for long duration infusion | 4.53 | 100 | Strong |
| It is safe to use gabapentin in PMD | 4.86 | 100 | Strong |
| It is safe to use phenytoin in PMD | 4.33 | 86.66 | Strong |
| It is safe to use levetiracetam in PMD | 4.86 | 100 | Strong |
| It is safe to use perampanel in PMD | 4.13 | 80 | Strong |
| It is safe to use topiramate in PMD | 4.46 | 100 | Strong |
| In refractory mitochondrial status epilepticus, propofol is safe for long duration infusion (up to 48 hours) | 4.47 | 100 | Strong |
| Ketamine is safe for long duration infusion (eg, refractory status epilepticus) in PMD | 4.31 | 93.75 | Strong |
| Bisphosphonates | |||
| It is safe to use bisphosphonates in PMD | 4.25 | 100 | Strong |
| Cardiovascular drugs | |||
| It is safe to use amiodarone in PMD | 4.06 | 93.3 | Strong |
| It is safe to use beta‐blockers in PMD | 4.46 | 100 | Strong |
| Enalapril is safe in PMD | 4.06 | 81.25 | Strong |
| Fibrate drugs‐Statins | |||
| It is safe to use fibrate in PMD | 4.62 | 100 | Strong |
| It is safe to use statins in PMD as long as guidelines concerning monitoring of CK and symptoms are followed | 4.5 | 100 | Strong |
Abbreviation: PMD, primary mitochondrial disease.