Tayside Area Formulary

Section 19 Drug Therapy in Relation to Anaesthesia  (reviewed Feb 06)

Refer to the local guideline Administration of Medicines in the Peri-operative Period, April 2011. (NHS Tayside Staffnet intranet link only)

INTRODUCTION

A complete record of current and recent drug therapy, and the occurrence of adverse drug reactions or evidence of drug abuse (including alcohol) must be clearly documented preoperatively. Current therapy should be reviewed and a decision to continue, adjust or withhold, before surgery should be made for each drug. 

Guidelines are provided in this section with specific advice on oral contraceptives, hormone replacement therapy (HRT), corticosteroids, oral anticoagulants, antiplatelet drugs and monoamine oxidase inhibitors. There is also an outline of the information which is essential for the anaesthetist in order to minimise the risk of any pathological response to drugs which might be administered during anaesthesia. 

Drug therapy which is commonly prescribed in the ward in relation to anaesthesia is discussed under the following headings: 

Premedication; Postoperative Analgesia; Anti-emetics; Reversal of Opioid Induced Respiratory Depression; Local Anaesthesia; and Sedation for Minor Surgical Procedures. 

Drugs for the above are included as part of the basic stock on all surgical wards. 

Important comments on the use of postoperative analgesia and intravenous sedation are included. 

For advice on diabetic therapy see Section 20 in this Formulary, “Guidelines for the Perioperative Management of Patients with Diabetes”. 

DRUG THERAPY IN THE PERIOPERATIVE PERIOD
Drugs used in the treatment of heart disease, hypertension, respiratory disease, epilepsy, Parkinsonism and thyroid disorders must normally be continued up to and including the morning of operation. 

The following may be continued, if necessary, but may cause problems related to anaesthesia: tricyclic antidepressants, lithium, levodopa (incl. Madopar, Sinemet), sedatives and tranquillisers. 

The drug therapy of thyrotoxicosis, myasthenia gravis, carcinoid syndrome and phaeochromocytoma require specialist management perioperatively. 

Oral Contraceptives and venous thromboembolic risk: The progestogen only pill (minipill) does not need to be discontinued but the combined (oestrogen-containing) oral contraceptives should normally be stopped for a least 4 weeks before and a minimum of 2 weeks after elective surgery in any of the following categories:

1. major surgery

2. minor or intermediate surgery when duration is likely to exceed thirty minutes and when mobilisation is unlikely until the following day eg tonsillectomy

3. surgery involving the lower limbs

4. surgery requiring hypotensive anaesthesia

5. surgery in a patient with significant additional thromboembolic risk factors, eg previous thromboembolic disease.

Instructions to stop oral contraceptive therapy must be accompanied by advice on the need for alternative contraception. Intramuscular medroxyprogesterone (Depo-Provera) may be appropriate in some cases. The patient’s GP must be consulted about appropriate contraceptive methods. 

If surgery must proceed without stopping the pill in a patient at risk, the reasons should be documented and appropriate DVT prophylaxis instituted.

Hormone Replacement Therapy (HRT): Hormone replacement therapy should be considered a risk factor for thromboembolism, but does not need to be routinely stopped preoperatively, as long as routine thromboprophylaxis is performed.  However, note that it is a licensing requirement of some HRT preparations that they be stopped prior to surgery.  Check the SPC for each product. 

Corticosteroids: If corticosteroids have been prescribed for longer than 2 weeks preoperatively or for more than one month in the previous year, perioperative cover may be required and the anaesthetist must be informed. Hydrocortisone 100mg intramuscularly one hour before surgery is commonly given and, after major surgery, may be repeated 6-hourly for 24-72 hours. It is important to monitor blood pressure postoperatively and to be aware of the possibility of hypoglycaemia, particularly if steroid cover has not been given. 

Oral Anticoagulants: Oral anticoagulant medication should be stopped at least 4 days before surgery which may cause significant bleeding, particularly if not amenable to external pressure. Reversal, even with vitamin K, may take up to a week and the use of factor IX concentrate may be necessary (see below). If anticoagulation is required for prophylaxis perioperatively, a low molecular weight heparin should be used (Fragmin 100iu/kg). Prolonged coagulation times, for whatever reason, is a contraindication to the use of spinal epidural anaesthesia. If in doubt contact the anaesthetist for guidance and advice.   

Emergency Reversal of Oral Anticoagulant Therapy: If a patient requires emergency surgery and is at high risk of bleeding (particularly intracranial or spinal bleeding) current expert opinion recommends administration of factor IX concentrate (contains factor II, IX and X – Defix^® produce by the Scottish National Blood Transfusion Service) and also factor VIIa concentrate if it is available.  Fresh frozen plasma does not correct factor IX deficiencies and so is less effective.  

Aspirin and NSAIDs: There is no evidence that these drugs increase the risk of vertebral canal haematoma formation associated with spinal or epidural anaesthesia. It is therefore not necessary to stop these medications preoperatively. However aspirin or NSAIDs may increase the risk of bleeding if low molecular weight heparin is used for  thromboprophylaxis. Again discuss with the anaesthetist and surgeon. 

Clopidogrel:  This potent antiplatelet drug is licensed for secondary prevention of thromboembolic events in patients with high risk coronary or cerebrovascular disease. Its effects on platelet aggregation are irreversible so platelet function will not completely return to normal for 7-10 days after stopping the drug (the time taken for a new platelet population to be produced). Clopidogrel has been associated with serious bleeding events in surgical patients and should be stopped at least 7 days before surgery. If an antiplatelet effect is required, low dose aspirin can be substituted (75mg daily). Discuss patients with coronary stents taking clopidogrel with a senior cardiologist. 

Monoamine Oxidase Inhibitors: Major adverse effects can result from the interaction of MAOIs with many drugs used in relation to anaesthesia, premedication and postoperative analgesia. 

Pethidine should also be avoided. 

Psychiatric advice should be sought and, whenever possible, MAOIs discontinued for at least 3 weeks prior to elective surgery.  

ABNORMAL RESPONSE TO DRUGS USED DURING ANAESTHESIA
It is necessary to ascertain preoperatively whether the patient, or a relative, has ever experienced problems with anaesthesia in the past. As well as adverse drug reactions, it is important to identify the possibility of atypical pseudocholinesterase (Scoline apnoea) or malignant hyperpyrexia. These are genetically inherited conditions so a careful family history should be sought. 

Renal failure, hepatic failure and porphyria are also important because of their possible effect on the pharmacokinetics of anaesthetics and related agents. 

PREMEDICATION

Temazepam 10mg tablets

Temazepam 10mg in 5ml solution

Lorazepam 1mg and 2.5mg tablets

Alimemazine/Trimeprazine tartrate 30mg in 5ml mixture (paediatric use)

Atropine sulphate 600microgram in 1ml injection

Midazolam oral liquid (paediatric use - unlicensed special) 

Non-steroidal anti-inflammatory drugs (see core list - Pain Control) are also sometimes prescribed as part of the premedication to enhance postoperative analgesia. 

POSTOPERATIVE ANALGESIA

Oramorph as per ward protocols 

Morphine sulphate 10mg in 1ml injection (0.06-0.2mg/kg IM) 

Morphine sulphate 50mg in 50ml sodium chloride 0.9% (normal saline) (for use in patient controlled analgesia pumps) 

Diamorphine HCI 5mg and 10mg in 1ml injection (0.03-0.1mg/kg IM) 

Oxycodone m/r tablets 5mg, 10mg, 20mg, 40mg, 80mg  

Oxycodone capsules 5mg, 10mg, 20mg, liquid 5mg/5ml 

Pethidine 50mg in 1ml injection (0.5-1.5mg/kg sc) (paediatric wards only) 

Diclofenac 25mg and 50mg tablets, 50mg and 100mg suppositories
(75-150mg daily in divided doses max 150mg daily) (NSAID - See warning below) 

Dyloject (diclofenac) 75mg/2ml injection - click here for link to dyloject protocol

Dihydrocodeine 30mg tablets

Co-codamol 30/500 tablets (codeine phosphate 30mg + paracetamol 500mg.

Paracetamol 500mg tablets  

Paracetamol 1g/100ml IV infusion

Paracetamol 250mg in 5ml oral suspension

Paracetamol 120mg in 5ml mixture (paediatric wards) (max paediatric dose: 90mg/kg/day for max of 48 hrs). 

Warning: Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided or given with extreme caution in patients at risk from the adverse effects on haemostasis and renal function, as well as those with a history of bronchospasm or peptic ulceration. Avoid NSAIDs in hypovolaemic or dehydrated patients because of risk of renal failure. 

POSTOPERATIVE ANALGESIA
Special consideration with regard to pain control:   

·  All patients should have regular formal assessment and charting of pain score.

·   Pain scoring should be routine.

·  Oral analgesia should be used whenever possible

·  Individual requirements and patient sensitivity vary greatly.  The initial prescription depends on body weight, but must also take into account age, sex, build, physical condition and known tolerance.  Assess patient frequently and review dosage of analgesia if appropriate.

·   Intramuscular injections act within 15-30 minutes and the peak occurs at 45-90 minutes.  The next injection must always be given when pain is beginning to increase again and it is important that nursing staff monitor patients accordingly.

·  Intravenous opioids should be administered in order to gain control of severe pain. The peak effect after intravenous injection occurs within 20 minutes. The dose is usually 1/5th (one-fifth) of the intramuscular dose (eg 2mg morphine).  To aid accurate measurement of a small IV bolus morphine dose, the injection may be diluted to a suitable volume before use with water for injection or 0.9% sodium chloride injection.  For example, diluting 10mg in 1ml injection to 10ml, giving a concentration of 1mg in 1ml. The 2mg dose can be repeated every 10-15 minutes until adequate analgesia is achieved provided that the patient is properly assessed before each dose. 

Continuous intravenous or subcutaneous infusion of opioid, patient-controlled analgesia (PCA), or regional analgesia may be required.  Continuous infusion of opioid, PCA and regional analgesia should only be instituted by staff who have received special instruction and have appropriate experience in their use and where there is adequate nursing supervision of patients.   

Advice relating to the management of acute pain, including the use of PCA, may be obtained from the Acute Pain Sister (bleep 4311 Ninewells, 5163/5180 PRI) or the Ninewells duty anaesthetist (bleep 4017), who may be contacted through the Department of Anaesthetics.  In addition, there is always a Senior Registrar or Consultant in Anaesthesia available to give advice on acute pain management.  At present, the Acute Pain Nurse conducts daily visits to postoperative wards to assess and follow up patients on PCA. 

Epidural infusion Analgesia (EIA) is currently limited to the ICU (PRI & Ninewells), High Dependency Unit (HDU Ninewells) and wards 7,8 and 16 at Ninewells. Nurses who work in these areas should undergo the competency based epidural training package which is locally available. A combination of local anaesthetic and opioid is infused into the epidural space.  Potential side effects include hypotension, loss of motor function in the legs and late respiratory depression, up to 24 hours after the infusion has been stopped.  A detailed protocol is available in the HDU. 

Continuous Peripheral Nerve Blocks: Techniques such as continuous sciatic nerve, brachial or lumbar plexus blocks are useful for major limb surgery such as arthroplasty or amputation. A catheter is placed close to the relevant nerve plexus by an anaesthetist and the block can be prolonged by either intermittent top ups or continuous infusions of local anaesthetic drugs (the anaesthetist is responsible for this). Local anaesthetics such as Ropivacaine or Levobupivacaine are typically used. Disposable infusion pumps are often used to deliver the fixed rate LA infusions. Any queries about these techniques should be directed to the acute pain team or anaesthetist. 

ANTI-EMETIC DRUGS (Postoperative) 

Cyclizine 50mg IM/IV bolus 

Ondansetron 4mg in 2ml IV/IM injection
(to be used for resistant postoperative nausea and vomiting (PONV), or in children with PONV - dose 0.1mg/kg, max 4mg) 

Prochlorperazine 12.5mg in 1ml injection
(by deep IM injection only; do not administer intravenously or subcutaneously) 

Prochlorperazine 3mg buccal tablets (Buccastem^®) – 1-2 tablets twice daily placed on buccal mucosa. 

COMBINED ANALGESIC AND ANTI-EMETIC THERAPY 

Morphine tartrate 10mg and cyclizine tartrate 50mg in 1ml injection (Cyclimorph-10) 

Note: It is recommended that administration of this combination be limited to 3 doses per 24 hours because of the risk of cyclizine overdosage. This may not provide adequate analgesia and further injections of morphine only should be used to provide additional pain relief. 

Adding cyclizine 50-100mg to PCA morphine syringes has been found to be ineffective in local audit and is therefore no longer recommended.  

REVERSAL OF OPIOID-INDUCED RESPIRATORY DEPRESSION 

In opioid overdosage, oxygen should be administered immediately according to the principles outlined in “Oxygen Therapy in Acute Management”.

Naloxone HCI 400microgram in 1ml injection. 

Note: If naloxone is given slowly by small intravenous increments (eg 100microgram), it is usually possible to overcome respiratory depression without complete reversal of the opioid’s analgesic effect. Note also that the duration of action is shorter than that of the opioid and repeated administration may be necessary. If the patient is unconscious a crash call (2222) should be put out to immediately summon skilled assistance. 

LOCAL ANAESTHESIA 

Infiltration anaesthesia:
Lidocaine/Lignocaine HCI 1% (10mg/ml), 10ml ampoule (maximum dose = 2mg/kg) 

Bupivacaine 0.25% (2.5mg/ml), 0.5% (5mg/ml). Amide local anaesthetic. Longer onset time and duration compared with lidocaine/lignocaine. Maximum dose is 2mg/ml. Great care must be taken to avoid accidental intravenous dosing as this may result in life-threatening local anaesthetic toxicity. 

SEDATION FOR MINOR SURGICAL PROCEDURES 

Midazolam 10mg in 5ml injection. 

Note that the potency is approximately twice that of diazepam and the 2mg/ml solution is advisable. Intravenous midazolam should be titrated, with great care, in 1mg increments (0.5mg increments in the elderly) at 2-minute intervals and verbal contact with the patient should be maintained. It must be stressed that caution is necessary in the elderly, as respiratory depression and profound sedation can occur with small doses. 

NB Heavy sedation is equivalent to general anaesthesia and should be supervised by a specialist.

Dr M Checketts, revised November 2005

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