El caso de Honduras 54

Most patients who have not had opiates before suffer from nausea and vomiting, especially when ambulatory. An anti-emetic like cyclizine or prochlorperazine should be prescribed at the same time as any opiate.

All opiates can cause respiratory depression; this is dependent on their •

potency and the dose used. Care should be taken in those patients with a decreased respiratory reserve.

All opiates can also cause constipation, including codeine, so it is •

advisable to prescribe laxatives at the same time as opioids. A stimulant laxative such as senna and a stool softener such as sodium docusate should be used. Beware of patients with an acute abdomen as the purgative effect may result in perforation.

All opiates can cause behavioural toxicity, particularly dysphorias. This •

may be a problem especially in older patients.

Doses of opiates should be appropriate to the patient, their body •

weight, and any concomitant disease. All patients should be monitored for effi cacy and side effects:

start with low doses in the elderly and debilitated patient •

use low doses or avoid opiates in patients with renal or hepatic •

impairment

avoid the use of opiates in patients with a head injury or raised •

intracranial pressure (can interfere with pupilliary responses). Anti-emetics

There are four main classes of agents used as anti-emetics: anticholinergics, antihistamines, dopamine antagonists, and 5HT3 antagonists. However, because of the many ways in which the vomiting centre can be triggered, no single medicine or class of medicine is completely effective in control- ling post-operative nausea and vomiting.

Anticholinergic drugs inhibit stimulation of the vomiting centre by blocking the action of acetylcholine at the muscarinic receptors in the vestibular system. They also reduce gastric motility and afferent stimulation of the vomiting centre.

Antihistamines such as cyclizine are suitable alternatives to pro- chlorperazine and metoclopramide, although not as effi cacious. They can cause drowsiness and often show anticholinergic side effects such as dry mouth and blurred vision.

Anti-emetics, which block central dopamine receptors (e.g. metoclo- pramide and prochlorperazine), can cause signifi cant behavioural toxicity, sedation, and acute dystonic reactions. These facial and skeletal muscle spasms are more common in the young, in females, and in elderly and debilitated patients. They tend to occur soon after therapy has started. The dystonias, such as oculogyric crisis or torticollis, can be treated if severe by parenteral antimuscarinics, e.g. procyclidine or benzatropine. Other extrapyramidal side effects can occur on prolonged therapy, e.g. Parkinsonian symptoms with tremor and akathesia. 5HT3 antagonists, such as ondansetron, are useful as second- or third-line therapy in patients who cannot tolerate standard antinauseants, and they also have a specifi c

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COMMONLY USED PERI-OPERATIVE DRUGS

use in cytotoxic chemotherapy. They should be considered as prophylaxis in patients known to be at risk of a decreased level of consciousness (oral surgery), or who have a history of uncontrolled post-operative nausea and vomiting.

Non-steroidal anti-infl ammatory drugs (NSAIDs)

Although these medicines are devoid of the respiratory depression and drowsiness caused by opiates, and are very effective analgesics, there are specifi c safety concerns, especially with their long-term use.

NSAIDs cause gastric irritation and should be avoided in patients with active peptic ulceration who are at an increased risk of haemorrhage or perforation. NSAIDs are contraindicated in patients with a history of hypersensitivity (asthma, urticaria, angioedema, and rhinitis) to aspirin or other NSAIDs and in patients with infl ammatory bowel disease.

Caution is required with the use of NSAIDs in patients with renal, hepatic, or cardiac impairment, as NSAIDs may cause a decrease in renal function. Patients also taking angiotensin-converting enzyme (ACE) inhibitors (e.g. captopril, enalapril, lisinopril) may be at a higher risk of renal impair- ment due to a drug interaction.

When used intravenously, additional contraindications include bleeding diathesis, operations with a high risk of haemorrhage, history of confi rmed or suspected cerebrovascular bleeding, history of asthma, hypovolaemia, and dehydration.

NSAIDs are more effective when used regularly rather than on a PRN basis. They have a useful opiate-sparing effect and have additive effects in combination with simple analgesics such as paracetamol.

Paracetamol/opiate combinations

In order to gain maximum benefi t from paracetamol it is better to use it on a regular basis rather than a ‘when required’ regimen. If the patient is in constant pain, paracetamol is very effective when used either as a stand- alone medicine or when used in combination with other simple analgesics or opioids.

Combinations of paracetamol with a low-dose opiate, such as dihydro- codeine and codeine, are popular as minor to moderate analgesics. However, the evidence for the effi cacy of adding low-dose opiates to paracetamol is limited and controversial. Increasing the dose of opiates will of course improve effi cacy and allows easy dose titration of doses but the unwanted side effects of opiates may still occur as discussed earlier. Thromboprophylaxis

Consider appropriate therapeutic and mechanical measures to prevent deep vein thromboses (DVTs) and pulmonary embolism (PE). The use of either unfractionated heparin or low molecular weight heparin (LMWH) should be encouraged. Costs of both are approximately equal; LMWH may be slightly more effective, especially in orthopaedic surgery, and is easier to administer once a day. Thromoprophylaxis measures should be adopted in line with national guidelines, which are available from NICE and the Department of Health.

152

Complications of medicines in surgery

IV therapy

Correct fl uid replacement is vital if a patient is NBM. However, the volume and type of fl uid should be appropriate. Total volume, tonicity, and electrolyte content are important.

Requirements

For an 80kg adult this equates to 2–3 litres a day, incorporating 150mmol of sodium and 40–60mmol of potassium. This maintenance therapy can be achieved by prescribing 1 litre of sodium chloride 0.9% infused over 8 hours followed by 1–2 litres of dextrose 5% each infused over 8 hours. Both dextrose 5% and sodium chloride 0.9% are available with 20mmol/l or 40mmol/l of potassium chloride.

Prescribing

It is good practice to prescribe each individual bag of IV fl uid separately on the fl uid prescription chart. This forces a daily review of IV fl uid therapy. IV fl uids should be prescribed on the current day’s chart: ‘fl icking’ back over previous charts to fi nd the next solution can result in adverse events. Systems that allow a prescription to cover an unlimited period of admin- istration are inherently dangerous, and can lead to unintentional fl uid overload. Fluid overload in the elderly with concomitant congestive heart failure can be fatal. Note that a number of medicines (IV and oral) contain quite large amounts of sodium, which need to be considered when calcu- lating electrolyte requirements.

Intravenous additives

IV therapy, which involves a sealed sterilized system (i.e. a bag of infusion fl uid) is generally safe and free from contamination. However, all bags should be inspected for the presence of particles or other contamina- tion, including if the bag has crystallized or if it is a different colour from normal.

Once sealed systems are breached, e.g. by adding medicines to a bag of fl uid for infusion, then microbial contamination becomes a potential problem. The physical and chemical stability of adding medicines and nutrients to infusion fl uid is of key importance, and if in doubt you should always refer for confi rmation of additions to pharmacy.

The guidelines are:

Only add a medicine to an infusion if it is really necessary (i.e. constant •

plasma concentration required; avoidance of a high, potentially toxic plasma concentration; dilute concentration required to avoid local tissue damage).

Always use a commercially available preparation if suitable •

(e.g. dopamine and potassium infusions are available premixed and sterilized).

Use a strict aseptic technique, wash your hands, and use gloves. •

All preparations should be freshly made and used immediately. •

After adding additives, shake the infusion well. Some additives are •

denser than the infusion fl uid and can settle unseen at the bottom of an infusion bag. This readily happens with potassium chloride solutions,

153

IV THERAPY

and can result in a bolus of all of the additive being infused – with potentially lethal consequences.

After adding additives check for signs of incompatibility immediately •

and then periodically afterwards. Look for precipitates, colour changes, and hazy or cloudy solutions. Look in the bag and the intravenous line. Some incompatibilities are often only seen after the fl uid has mixed with other fl uids being infused at the same time through Y sites, for example.

Clearly label the infusion solution with the name of the medicine, •

the amount added, the date and time of addition, the patient’s name, and the date and time of expiry. Labels designed for this are usually available from the pharmacy.

Always seek expert advice from the pharmacy as some medicines are •

inherently unstable.

Wherever possible use a centralized intravenous additive service. •

Contamination of parenteral fl uids is a problem from which patients still suffer morbidity and mortality.

Total parenteral nutrition (TPN) is expensive, complicated to •

make, and is an ideal medium for the growth of microorganisms if contaminated. The compounding of TPN should be carried out within the pharmacy under strict aseptic conditions.

Never add medicines to blood, albumin, colloids, mannitol solutions, •

sodium bicarbonate, or lipid solutions due to the risk of instability or haptan formation.

Some IV medicines are chemically incompatible when when given •

together, e.g. infused through a ‘Y’ connector. Check with the pharmacy before running IV medicines together.

The BNF contains much useful information on this topic. Using the oral route of administration

The IV route of administration is obviously mainly used peri-operatively. However, consider switching to oral as soon as possible. The oral route reduces the risk of adverse events, decreases the administration work- load, and reduces the cost, but is only to be used when the gut is effective. Oral and IV doses are not always interchangeable. Check with the BNF/ pharmacy if unsure.

Antibiotics

Antibiotic guidelines for treatment and prophylaxis should be agreed, implemented, and subjected to regular updates and audits.

Principles of antibiotic prophylaxis

The decision regarding the benefi ts and risks of prophylaxis for an indi- vidual patient will depend on:

the patient’s risk of surgical site infection •

the potential severity of the consequences of surgical site infection •

the effectiveness of prophylaxis in that operation •

the consequences of prophylaxis for that patient (e.g. increased risk of •

154

Complications of medicines in surgery

Selection of agent should refl ect professional body recommendations, local antibiotic sensitivities, drug costs, and consultant experience.

The selected antibiotic for prophylaxis must cover common pathogens. •

Patients with a history of anaphylaxis, urticaria, or rash occurring •

immediately after penicillin or cephalosprin therapy are at an increased risk of immediate hypersensitivity and should not receive prophylaxis with a beta-lactam antibiotic.

In order to keep the risk of surgical site infection to a minimum antibiotic prophylaxis should be administered to ensure maximum blood and tissue levels coincide with the time of surgical incision. The timing of the fi rst dose is crucial and should be up to 60 minutes prior to incision. An ideal time would be to give the antibiotic at the same time as the induction of anaesthesia.

In most cases prophylactic antibiotics should be administered •

intravenously.

An additional dose of antibiotic may be indicated if surgery is prolonged •

or there is blood loss during surgery of 1500ml or haemodilution of up to 15ml/kg.

For most procedures requiring antibiotic prophylaxis, a single dose is •

satisfactory.

Prophylaxis should not normally extend beyond 24 hours after the •

procedure.

Fluid replacement bags should not be primed with prophylactic •

antibiotics because of the potential risk of contamination and calculation errors.

Treatment of infections

Antibiotic regimens for treatment should be:

Targeted at the pathogens likely to cause surgical site infections. •

Chosen according to culture and sensitivity results and local sensitivity •

patterns for likely organisms.

Of short duration to minimize adverse drug reactions and reduce •

antibiotic resistance, Clostridium diffi cile infection, and environmental exposure.

Reviewed daily and switched to an oral equivalent at the earliest •

opportunity. Patients who are colonized should not be treated unless they have signs of an active infection.

155

SURGERY ALTERING THE PHARMACOKINETICS OF MEDICINES

Surgery altering the pharmacokinetics