Neobook — clinical reference

Clinical guidelines on the use of patient-controlled analgesia

PCA and neuraxial analgesia techniques offer alternative nonconventional methods for postoperative pain management.

Clinical guidelines on the use of patient-controlled analgesia

Rationale for use

PCA refers to a method of analgesia through which a patient self-administers small doses of an analgesic, usually an opioid, delivered with a programmable infusion pump.

Efficacy

The proposed benefits of PCA, compared to conventional parenteral opioid regimens, include the following:

Improved pain control
Higher patient satisfaction
Decreased risk of overdose
Less labour-intensive for the nursing staff

However, IV PCA with opioids may result in higher opioid consumption and pruritus compared to intermittent opioid administration. There may also be no difference in efficacy in settings with a high nurse-to-patient ratio.

The decision to provide PCA depends on availability and resources (financially and staffing), and is taken after discussion with the patient. Ongoing communication regarding, for example, the adjustment of demand dosing, may influence the success of PCA management.

PCA is only effective after the initial rapid pain control under supervision of the prescribing physician, for example, in the postoperative care unit. Initial doses should be individualised, taking into account factors such as previous opioid use and age.

The concept of PCA continues to develop in children. Patient-controlled epidural analgesia (PCEA), SC PCA and intranasal (IN) PCA are extensions of this method. PCA, when used with adequate monitoring, is a well-tolerated technique with high patient and staff acceptance. It can now be regarded as a standard for the delivery of postoperative analgesia in children above the age of 5 years.

Cost

Although equipment cost is higher, the possible benefits of reduced adverse effects and nursing time must also be considered.

Standards of care

The safety of PCA can be improved upon by adopting standardised protocols regarding methods and documentation (see Chart 1). Operator errors may be reduced with the use of ‘smart pump’ technology. Although technical device errors may be more common than operator errors, very few technical errors seem to be associated with patient harm.

Chart 1: Proposed prescription chart

Prescription chart
Instructions

Nursing staff are not allowed to change settings on the pump
PCA boluses must only be administered by the patient, not by the nursing staff

Click on the image to enlarge

Additional instructions

Clinical practice points

The changing pain score and the presence of side effects should be detected through appropriate routine monitoring of patients, in order to prevent complications such as an inadvertent overdose or inappropriate use (e.g. nurse or doctor administration of the intended PCA bolus). The masking of pain from new problems, such as compartment syndrome of the limbs, urinary retention, pulmonary embolism (PE) or myocardial infarction, should also be uncovered.
Monitoring addresses the prevention of complications, and assures that repeated assessment is conducted with regard to the adequacy of pain management.

Figure 1: Proposed treatment algorithm for patient-controlled analgesic management (adapted, not revised; used with permission)

3. Intensive and frequent monitoring is essential in patients at risk of developing respiratory depression and other side effects. If peripheral oxygen saturation cannot be continuously monitored, administering oxygen by nasal cannula or face mask for the duration of IV opioid administration may be indicated.

4. Standardised prescriptions within institutions also prevent complications arising from the use of supplemental medication, such as opioids by other routes, or sedatives (see Table I).

5. A standardised treatment algorithm may improve pain management by integrating pain assessment and side effects with a clear reaction pathway. A treatment algorithm for PCA management is detailed in Figure 1.

Medication

Opioid analgesics

Generally, there are no major differences in the efficacy of various opioid drugs for PCA. On an individual basis, one opioid may be better tolerated than another, and it may be beneficial to change to an alternative agent if a patient is experiencing intolerable side effects.

The following opioid analgesics are available for PCA use in South Africa:

IV morphine: Included in the adult hospital level Essential Medicines List. A background infusion increases the risk of respiratory depression with no additional benefit.
IV tramadol: Recommended for inclusion in the adult hospital level Essential Medicines List, for regional hospitals only. It provides effective analgesia comparable to morphine.
IV pethidine: Pethidine should not be prescribed. It may cause neurotoxicity owing to the accumulation of norpethidine.
IV remifentanil: Offers analgesia equivalent to morphine and may be associated with less nausea and vomiting.
IV fentanyl: There is limited evidence of a difference between IV fentanyl and morphine.
IV oxycodone: It has similar effects to morphine.

Adjuvant medicines in PCA

The opioid dose-sparing effect of concurrent NSAIDs, ketamine, pregabalin, lignocaine, clonidine and dexmedetomidine, may contribute to a reduction of opioid adverse effects. The following adjuvant medicines may be added to the opioid solution.

Antiemetic drugs

The routine addition of antiemetic drugs to a PCA infusion is not advocated as there is no additional benefit over selective administration when indicated.
Droperidol is an effective antiemetic, but may cause unacceptable sedation at the dose necessary to prevent nausea and vomiting.
The benefit of adding 5-hydroxytryptamine-3 antagonists (e.g. ondansetron) to PCA, is unclear. 5-HT-3 receptor antagonists should not be used with tramadol.

Ketamine

The addition of ketamine to PCA may benefit patients after major surgery with regard to analgesia as well as the adverse effects of opioids.

Dexmedetomidine

There is some evidence that the use of dexmedetomidine, when added to IV morphine PCA, may improve analgesia and reduce morphine-related side effects without increasing sedation or the haemodynamic side effects.

Hydroxyzine

There is no evidence to support the addition of hydroxyzine to PCA.

Equipment and programme variables/settings

Several PCA products are available in South Africa. Systems can be broadly categorised into the following two groups:

Durable (often bulky) pumps with disposable cartridges, which usually offer multiple programmable options.
Pumps composed of disposable components with built-in mechanisms for bolus administration. These do not allow background infusion administration or provide programmable options.

The effectiveness of the latter systems may be compromised by the fact that dose adjustments cannot be made, although these may provide a cost benefit.

All PCA infusion systems must incorporate anti-syphon valves, as well as anti-reflux valves in nondedicated lines

Pump settings

Bolus dose

The optimal bolus dose should provide adequate pain relief with minimal adverse effects. Age and a history of previous opioid exposure can influence the response to the bolus dose. The usual PCA bolus dose for morphine is 1 mg (15–20 µg/kg).

Lockout time

The lockout time interval should allow the analgesic to reach its peak effect. The optimal lockout time for morphine is 7–11 minutes.

Dose limits

An overdose with PCA is usually due to the effect of large doses accumulating after hours or days. Limiting the maximum dose over several hours may be the most effective way of preventing an overdose. However, sound evidence of a benefit that can be attributed to these limits, does not exist. The impact of decreased clearance should be kept in mind (e.g. liver impairment, kidney failure, cardiac failure and any cause of a decreased cardiac output).

Background infusions

The risk of respiratory depression is higher when a background infusion is used, and it does not improve pain control or sleep, or reduce the number of PCA demands. It may be useful in opioid-tolerant patients, but its routine use is not advised.

Loading dose

No good evidence of any benefit exists when using this option on programmable pumps. Pain should be controlled first by titrated LDs before PCA is started.

Total amount and concentration

Drug concentrations should be standardised within institutions to reduce the occurrence of programming errors.

Examples of PCA management regimens are provided in Table I.

Table I: Examples of IV patient-controlled analgesia management regimens

Morphine with Opioid dilution of 1 mg/ml
Additive	Additive dilution	Pump settings for opioid
Dexmedetomidine or ketamine droperidol or ondansetron	2–5 μg/ml 2 mg/ml 15–100 μg/1 mg morphine, or 5 mg/100 ml 16 mg/100 ml	- Bolus of 1 mg (1 ml) - Lockout time of 7–11 minutes - Maximum 30 mg in 4 hours
Tramadol with Opioid dilution of 5 mg/ml
Additive	Additive dilution	Pump settings for opioid
Dexmedetomidine	1–2 μg/ml	- Bolus of 10–20 mg - Lockout time of 5–10 minutes

Table I continued

Opioid	Opioid dilution	Pump settings for opioid
Remifentanil	50 μg/ml	- Bolus of 50 μg over 5 minutes (background 0.075– 0.15 μg/kg/ minute) - Lockout time of 5 minutes
Sufentanil	1 μg/ml	- Bolus of 4–6 μg (background of 1.15 μg/hour) - Lockout time of 1 minute
Fentanyl	1 μg/ml	- Bolus of 30–40 μg - Lockout time of 5–8 minutes - Maximum 300 μg in 4 hours

Neuraxial techniques

Epidural analgesia

Epidural analgesia (i.e. the provision of pain relief by the continuous administration of agents into the epidural space via an indwelling catheter) has become a widely-used technique for the management of acute pain in adults and children. Epidural analgesia at the correct level for an appropriate duration may decrease pulmonary complications, ventilator requirements or MI, and may improve bowel motility. However, data on improved outcomes are controversial, and the focus should be on pain relief and patient satisfaction.

Clinical practice points regarding epidural analgesia

The decision to perform an epidural, and the technique selected, should be appropriate for the intensity of pain anticipated and congruent to the level of tissue damage (i.e. head and neck, torso or limbs).
All techniques of epidural analgesia, except when using a lipophilic opioid only, for all types of surgery, provide better postoperative pain relief than parenteral opioids (including PCA).
The complete absence of pain is seldom achievable, and never realistic, even with neuraxial techniques. The objective should therefore be the balance between analgesia, patient satisfaction, safety and available resources. A VAS count of < 4/10 (40/100) is usually a satisfactory goal.
Combinations of low concentrations of LAs and opioids provide better analgesia than either component alone, and reduce the dose requirements of both drugs.
Permanent neurological damage with epidural techniques is a rare, but devastating, occurrence and all efforts should be made to prevent, diagnose and treat it immediately. Immediate decompression of a haematoma or an abscess increases the likelihood of recovery. Therefore, the risks and benefits should be discussed with the patient and informed consent obtained.
The insertion of an epidural catheter at spinal level matching the dermatome of the surgery (i.e. catheter incision-congruent analgesia) results in optimal postoperative epidural analgesia by infusing analgesic agents to the appropriate incisional level, providing superior analgesia and minimising side effects.
Infusions of epidural LA plus opioid combinations in a general ward have been advocated to be safe, but the precondition is supervision by an anaesthesia-based pain or similar service, with 24-hour medical staff cover, and monitoring by well-trained nursing staff. In many hospital wards, this may not be available or possible.
Epidural catheters are inserted under sterile conditions for obvious reasons. A sterile theatre gown, mask, cap and gloves must be worn. It is prudent to use an alcoholic chlorhexidine solution to disinfect the skin, adhere to antiseptic technique at insertion, maintain sterility at the puncture and infusion ports, and to remove the catheter before or on day five. Chlorhexidine-impregnated dressings of epidural catheters reduce the incidence of catheter bacterial colonisation. Whenever the epidural filter gets disconnected from the catheter, both the filter and the catheter must be regarded as contaminated and the epidural catheter must be removed.
The level of the epidural is determined by the level of trauma. The benefits of postoperative epidural analgesia are optimised when the epidural catheter is inserted in a location which corresponds to the dermatomes covered by the surgical incision (i.e. catheter incision-congruent analgesia) resulting in a lower dose of the drug being administered and a decreased incidence of drug-induced side effects, such as pruritus, nausea, vomiting, urinary retention, motor block and hypotension. Although an incision-congruent level of block supplies somatic analgesia, visceral analgesia requires a block that includes a few segments above and below the incision level (Table II). According to NYSORA, a generally accepted guideline for dosing epidural anaesthesia in adults is 1–2 ml per segment to be blocked.

Table II: Level of the epidural

Surgery	Level of the epidural
Thoracotomy	T4–T8
Upper abdominal	T6–T8
Middle abdominal	T8–T10
Lower abdominal	T8–T12
Lower extremity	L1–L4

Epidural local anaesthetics

LAs available for epidural use in South Africa are outlined in Table III.

Table III: Local anaesthetics for epidural use available in South Africa

Duration of action	Drug	Formulation
Short-acting	Lignocaine	Various
	Bupivacaine	Macaine® 0.5% (5 mg/ml), with or without adrenaline Macaine® 0.1% (1 mg/ml) polybag
Long-acting	Levobupivacaine	Chirocaine® 5.0–7.5 mg/ml
	Ropivacaine	Naropin® 5.0, 7.5 and 10 mg/ml, and 2 mg/ml as the 100/200 ml polybag

There are no consistent differences between ropivacaine, levobupivacaine and bupivacaine when given in low doses for regional analgesia in terms of quality of analgesia and motor blockade.

Epidural opioids

The behaviour of epidural opioids is governed largely by their lipid solubility. Morphine is the least lipid soluble of opioids administered epidurally. As it has a prolonged analgesic effect, it can be given either by intermittent bolus dose or by infusion. With bolus dose regimens, the risk of respiratory depression is higher and analgesia is less effective. Lipophilic opioids (e.g. fentanyl, sufentanil and alfentanil) have a faster onset, but shorter duration of action, compared with hydrophilic drugs. Contrary to epidural morphine, epidural lipophilic opioids reach analgesic systemic concentrations, which contributes substantially to their analgesic effects.

The levels of the required level of the epidural blocks are outlined in Table II.

Epidural test doses

This procedure is standard when the epidural commences, but should be repeated before top-up doses for analgesic purposes. Although migration of the catheter to the intravascular or intrathecal space from the epidural space is uncommon, aspiration and the administration of a test dose of adrenaline and LA before bolus dosing for pain may prevent complications (e.g. high or total spinal anaesthesia and neurotoxicity) associated with the accidental administration of LAs into this space. After negative aspiration, 45 mg of lignocaine plus 15 µg of adrenaline, can be administered as a test dose. This is prepared as follows:

Adrenaline 2 mg is diluted to 10 ml = 20 µg/ml.
Add 1 ml of this adrenaline dilution (20 µg) to 3 ml of lignocaine 2% (20 mg/ml) in a 5 ml syringe. This solution contains 60 mg of lignocaine plus 20 µg of adrenaline in 4 ml. Therefore, 3 ml will contain 45 mg of lignocaine and 15 µg of adrenaline.
Since the dead space of the epidural catheter and filter is approximately 1 ml, 4 ml can be administered in a bolus. If the filter and catheter has been primed with the solution, 3 ml is administered.

According to NYSORA: “The intrathecal injection of 45 mg of lidocaine should produce a significant motor nerve block if the catheter is in the subarachnoid space, although recent evidence suggests that this is not always reliable. A change in heart rate of 20% or greater (or, alternatively, an increase in heart rate of 10 to 25 beats per minute) within 1 minute suggests that the catheter has been placed in (or has migrated into) a vessel and should be replaced. If the heart rate does not increase by 20% or greater or if a significant motor nerve block does not develop within 5 minutes, the test dose is considered negative. Exceptions to this rule have been observed in labouring patients, anaesthetised patients, and patients receiving β-adrenergic blocking agents.”

Patient-controlled epidural analgesia

The use of patient-controlled epidural analgesia (PCEA) is based on the individualisation of therapy, similar to other patient-controlled techniques. The optimal settings of PCEA will vary, based on the epidural vertebral level, type of surgery, as well as patient factors.

Systemic analgesia in combination with epidural analgesia

The use of epidural analgesia does not preclude the use of systemic analgesia. Patients with epidural analgesia should have concomitant paracetamol prescribed to treat other aches and pains, and facilitate the withdrawal of epidural analgesia.

Table IV: Complications of epidural analgesia treatment

Complications	Incidence	Treatment	Remarks
Nausea and vomiting	Common	Ondansetron or class equivalent, droperidol or prochlorperazine	Dose-dependent
Pruritus	Common	Antihistamine, naloxone or droperidol, HT3 receptor antiemetics (ondansetron, granisetron)	Dose-dependent
Urinary retention	Common	Catheterise
Postdural puncture headache	Uncommon, unless dura is perforated	Bed rest, intravenous fluids, caffeine, analgesics, neostigmine plus atropine If no improvement of symptoms within 48 hours, consider an epidural blood patch	A blood patch is controversial
Hypotension	Uncommon	IV volume Decrease the dose and rate of the epidural infusion	Prevent hypovolaemia
Motor block	Common with higher concentrations of LA	Decrease the dose of local anaesthetic	It may be more frequent with bupivacaine
Respiratory depression	Uncommon	If due to opioid: naloxone Supportive measures (see text below for specific interventions)	Sedation is an early warning sign Sedation can be caused by hypoventilation due to opioids, hypotension, high block, etc.
Local anaesthetic systemic toxicity (LAST)	Uncommon	LAST: intralipid CPR	Bupivacaine > levobupivacaine ≥ ropivacaine
Epidural haematoma or abscess	Rare	Surgical decompression within 8 hours	Urgent neurosurgical consultation and imaging to confirm the diagnosis
Permanent neurological damage	Rare	Prevent	Warn patient of risk before performing the procedure

LA – local anaesthetic, LAST – local anaesthetic systemic toxicity, CPR – cardiopulmonary resuscitation

Respiratory depression by epidural solutions

A strategy to detect and treat this complication should be in place. The incidence of respiratory depression is between 1% (decreased RR) and 15% (desaturation) depending on the criteria used, but is clinically significant in less than 1% of patients. High-risk patients (e.g. sleep apnoea and obesity) should be identified preoperatively.

Patients receiving neuraxial opioids should be monitored clinically for adequacy of ventilation, oxygenation and level of consciousness 1–2-hourly for the first 24 hours after injection with morphine, or continuously during an infusion. The absence of a decreased RR is not a reliable warning sign of respiratory depression, but it is almost always preceded by sedation. (Exclude motor block, high block, sympathetic nervous system block, migration of catheter, etc.)

Supplemental oxygen should be available to patients receiving neuraxial opioids, and administered to those with an altered level of consciousness, respiratory depression or hypoxaemia. In the infrequent event of life-threatening apnoea, the airway should be maintained, and the patient bag-mask ventilated pending naloxone administration. The naloxone dose should be titrated to effect (40–80 μg IV increments), followed by an infusion at a dose sufficient to maintain an adequate RR until the effect of the opioid has worn off (e.g. 1–2 μg/kg/min).

The reason for the respiratory depression should be assessed and the dose of the neuraxial infusion of opioids decreased if this is the cause. If an epidural infusion is stopped, alternative pain treatment should be prescribed to prevent rebound pain.

The patient should be transferred to a higher level of nursing for care and monitoring.

Duration of epidural analgesia

The epidural catheter is commonly left in place for 2–4 days, but it is impossible to scientifically determine what the maximum safe time would be to persist with a percutaneous catheter owing to the rarity of epidural infections.

Drugs and doses used in epidural analgesia are outlined in Table V.

Table V: Drugs and doses used in epidural analgesia

Lipophilic opioid infusion

Fentanyl
Dose	Onset	Duration	Remarks
Dilute the single dose in 10 ml normal saline: - Loading dose = 50–100 μg - Infusion dose = 25–100 μg/hour	5–10 minutes	2–4 hours	- Limited spread in CSF - Early respiratory depression is most likely - Opioids alone via the epidural route seem to be of limited benefit
Sufentanil
Dose	Onset	Duration	Remarks
Dilute the single dose in 10 ml normal saline: - Loading dose = 10–50 μg - Infusion dose = 10–20 μg/hour	5–10 minutes	2–4 hours	- Limited spread in CSF - Early respiratory depression is most likely - Opioids alone via the epidural route seem to be of limited benefit

Hydrophilic opioid infusion

Morphine
Dose	Onset	Duration	Remarks
Loading dose = 1–5 mg Infusion dose = 0.1–1 mg/hour	30–60 minutes	6–24 hours	- Extensive spread in CSF - Early and delayed respiratory depression is possible

Local anaesthetics

Bupivacaine*
Dose	Onset	Duration	Remarks
5–8 ml/hour of 1.25–2.5 mg/ml solution or incremental doses of 3–5 ml of 1.25–2.5 mg/ml solution	10–20 minutes 30 minutes for optimal effect	3–4 hours	- Establish the block with a 0.5% bolus of 15–30 ml - Recommendation: Limit to 2 mg/kg in 4 hours and 400 mg/24 hours
Levobupivacaine
Dose	Onset	Duration	Remarks
10–15 ml/hour of 1.25 mg/ml, or 5–7.5 ml/hour of 2.5 mg/ml		150–240 minutes	- Minimal to moderate motor block - Dilution stable for up to 7 days at 20°C - Maximum dose over 24 hours of 400 mg
Ropivacaine
Dose	Onset	Duration	Remarks
2 mg/ml Bolus:10–20 ml 6–14 ml/hour	15–20 minutes	140–200 minutes	Establish the block for surgery with 15–25 ml of 7.5 mg/ml for a lumbar epidural, or 5–15 ml for a thoracic epidural

* Not commonly used alone in an analgesic infusion, CSF – cerebrospinal fluid

Local anaesthetic-opioid infusions

Drug	Dose	Remarks
Ropivacaine 2 mg/ml + fentanyl 4 μg/ml	6–14 ml/hour	This combination is marketed as a polybag in some countries (not in South Africa)
Bupivacaine 1 mg/ml + fentanyl 4 μg/ml	5–10 ml/hour	Prepare by adding 20 ml of 0.5% bupivacaine to 40 μg fentanyl (4 x 100 μg ampoules) and 72 ml normal saline (total volume = 100 ml)
Bupivacaine 0.625 mg/ml +fentanyl 2–5 μg/ml	8–16 ml/hour

Local anaesthetic-opioid epidural PCA (infusion + demand)

Levobupivacaine 1.25 mg/ml + fentanyl 4 μg/ml
Continuous infusion (ml/hour)	Demand dose (ml)	Lockout (minutes)	Remarks
Initial rate of 4 ml/hour	2	10	Stability proven for up to 40 hours at 20°C
Bupivacaine 1 mg/ml + fentanyl 5 μg/ml
Continuous infusion (ml/hour)	Demand dose (ml)	Lockout (minutes)	Remarks
6 ml/hour (3–4 ml/hour for thoracic block)	2	10–15
Ropivacaine 1–2 mg/ml + fentanyl 2 –5 μg/ml
Continuous infusion (ml/hour)	Demand dose (ml)	Lockout (minutes)	Remarks
3–5 ml/hour	2	10–20

Spinal (intrathecal) analgesia

A single injection of intrathecal LA plus an opioid is an acknowledged part of a postoperative analgesia strategy. It is as effective as, or even better than, other established techniques, although the duration of the relief is limited to the first 24 hours and side effects are common.

Drugs used for intrathecal analgesia

LAs are often combined with opioids to provide a smooth transition from the anaesthetic technique to the analgesic plan.

Drugs for intrathecal analgesia are detailed in Table VI.

Table VI: Drugs for intrathecal analgesia

Drug (preservative free)	Intrathecal single dose	Onset	Duration
Fentanyl	5–25 μg	5–10 minutes	1–4 hours
Sufentanil	2–10 μg	5–10 minutes	2–6 hours
Morphine	50–300 μg	45–75 minutes	18–24 hours

The longer duration of morphine has established it as the drug of choice, but this advantage is gained at the increased risk of respiratory depression. At doses of 100–800 µg, intrathecal morphine for pain relief, following a range of surgical procedures, produces a high degree of patient satisfaction and effective analgesia during the first 24 hours. In particular, the lower dose of 100–200 µg offers effective analgesia, with a low risk of adverse effects (e.g. for hip replacement in the elderly). However, higher doses are required for thoracotomy and abdominal surgery. In general, there is a ceiling analgesic effect for doses above 200 μg. Significant side effects associated with intrathecal morphine are as follows:

Respiratory depression in 3% of patients (partial pressure of carbon dioxide [PaCO₂] ≥ 50 mmHg, and/or an RR ≤ 8/minutes)
Pruritus (itching) in up to 30% of patients
Nausea and vomiting in 25% of patients
Urinary retention in 35% of patients

When intrathecal morphine is administered, the patient should be nursed in an area where there is a high level of awareness of the risk of respiratory depression. The monitoring and treatment of these complications is similar to that employed with epidural opioids. The analgesic efficacy rivals that of PCA, but does not last for longer than a day. A multimodal plan of alternatives should be in place to prevent (preferably) or treat rebound pain. Lipophilic opioids may be suitable for outpatient surgery, but morphine is not.

Indwelling spinal catheters are not established as a routine technique for the treatment of short-term pain.

Clinical practice points

Intrathecal morphine offers improved analgesia and is opioid-sparing for up to 24 hours.
Intrathecal morphine doses of ≥ 300 µg increase the risk of respiratory depression.
The incidence of respiratory depression and pruritus after major surgery is higher with intrathecal morphine than with IV PCA opioids, but there is no difference in the incidence of nausea and vomiting.
The lowest effective dose should be used in all circumstances.

Neuraxial techniques and concurrent anticoagulant medication

Neurological compromise due to neuraxial haemorrhagic complications is rare, but devastating. It can be difficult to decide whether it is worth the risk to perform spinal or epidural procedures. The risk of haematoma is almost impossible to determine, but has been calculated at about 1:150 000 for epidural anaesthesia and 1:220 000 for spinal anaesthesia. Owing to the paucity of scientific evidence, the clinician has to rely on clinical judgement, consensus expert opinion and knowledge of pharmacology, to decide whether it is worth the risk to perform the spinal or epidural for anaesthesia per se, or as an analgesic technique. This risk is increased by the following factors:

Anticoagulation (the most important risk factor)
Any other coagulopathy
Advanced age (older than 65 years)
Female gender
Difficult needle placement
Abnormalities of the vertebral canal or spinal cord
Indwelling catheter techniques (especially during sustained anticoagulation)

Absolute recommendations cannot be made in many clinical situations and the opinions of experts in the field should be considered. For example, the Consensus Conference of the American Society of Regional Anesthesia and Pain Medicine can be found at http://www.asra. com.

Medications, indications and information continue to evolve. Knowledge should be current.

Every case should be individualised according to risk versus benefit in each particular situation. What may be feasible to the expert in a specialised environment may not be a worthwhile risk to the regular anaesthetist in routine practice. Err on the side of safety. Take care to prevent a combination of anticoagulation effects. Neuraxial techniques should not be performed in patients who receive more than one anticoagulant simultaneously (especially when early postoperative use of other anticoagulant drugs is anticipated).

It is prudent to raise the level of vigilance as the haemostatic compromise increases, and to evaluate the patient every two hours if the risk is deemed to be high. The most common presenting symptoms of a neurologically significant haematoma are a progressive sensory and motor block (68%) or bowel/bladder dysfunction (8%); however, severe radicular back pain is uncommon. Spinal cord ischaemia tends to be reversible in patients who undergo surgical decompression within 8 hours of onset of neurological dysfunction. The implication of this is that the anaesthetist cannot perform the neuraxial technique and consider that to be the end of their commitment to the patient’s care.

The novel oral anticoagulants have a long duration of action, and care must be taken when considering the timing of neuraxial anaesthetic. Generally, the decision whether or not to continue the anticoagulant up to the time of the surgical procedure, is made by weighing the risk of thrombosis if the anticoagulant is stopped versus the bleeding risk of the procedure. This should be a multidisciplinary discussion.

Recommendations on timing of neuraxial techniques after stopping the anticoagulant are usually pharmacologically based. For example, recommended time intervals between discontinuation of a drug during therapeutic anticoagulation and subsequent neuraxial block are 5 half-lives (and is dependent on renal function). This will allow for resolution of 97% of anticoagulant effect. With lower levels of anticoagulation associated with prophylaxis, only a 2-half-life interval is required. Subsequent dosing of anticoagulation therapy is based on 8 hours (the time it takes for a platelet plug to become stable) minus the time it takes the anticoagulant to reach peak effect.

It can be foreseen that inadvertent or unavoidable anticoagulation would be instituted in a patient with a neuraxial catheter in situ. In this case, the treating physicians should consider the safest compromise and optimal timing to remove the catheter.

A reasonable approach to the practical management of neuraxial anaesthesia and analgesia in the patient on anticoagulation medication is summarised in Table VII. The recommendations are not absolute and the risk versus benefit must be considered in every clinical scenario.

Table VII: Clinical approach to neuraxial analgesia in the patient on medication with anticoagulation effects

Herbal (ginkgo, garlic and ginseng)
Is epidural or spinal reasonable?	Yes
Time from last dose to neuraxial block insertion	Anytime
Administration of drug while catheter in situ	Can continue
Time from dose (while catheter in situ) to catheter removal	Anytime
Time from block/removal of catheter to next dose	Anytime
Remarks	Combination with others may be unsafe

NSAIDs (COX-2 inhibitors preferred)
Is epidural or spinal reasonable?	Yes
Time from last dose to neuraxial block insertion	Anytime
Administration of drug while catheter in situ	Can continue
Time from dose (while catheter in situ) to catheter removal	Anytime
Time from block/removal of catheter to next dose	Anytime
Remarks	Combination with others may be unsafe

Aspirin
Is epidural or spinal reasonable?	Yes
Time from last dose to neuraxial block insertion	Anytime
Administration of drug while catheter in situ	Can continue
Time from dose (while catheter in situ) to catheter removal	Anytime
Time from block/removal of catheter to next dose	Anytime
Remarks	Combination with others may be unsafe

Dipyridamole
Is epidural or spinal reasonable?	Yes
Time from last dose to neuraxial block insertion	Anytime
Administration of drug while catheter in situ	Can continue
Time from dose (while catheter in situ) to catheter removal	Anytime
Time from block/removal of catheter to next dose	≥ 6 hours
Remarks	Combination with others may be unsafe

Dipyridamole/ aspirin combination
Is epidural or spinal reasonable?	Yes
Time from last dose to neuraxial block insertion	24 hours
Administration of drug while catheter in situ	Stop combination drug, aspirin may be continued
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	≥ 6 hours
Remarks	Increased risk of bleeding with combination therapy

SC UFH prophylaxis (low-dose) ≤ 15 000 U/day
Is epidural or spinal reasonable?	Yes
Time from last dose to neuraxial block insertion	≥ 4–6 hours or confirm normal aPTT
Administration of drug while catheter in situ	Can continue
Time from dose (while catheter in situ) to catheter removal	≥ 4–6 hours or confirm normal aPTT
Time from block/removal of catheter to next dose	≥ 1 hour
Remarks	Consider HITT if ≥ 4 days on heparin, and perform a platelet count

SC UFH prophylaxis (high-dose) ≤ 20 000 U/day
Is epidural or spinal reasonable?	Caution advised
Time from last dose to neuraxial block insertion	≥ 12 hours and confirm normal aPTT
Administration of drug while catheter in situ	Safety not established
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	≥ 1 hour
Remarks	Consider HITT if ≥ 4 days on heparin, and perform a platelet count

SC UFH therapeutic ≥ 20 000 U/day
Is epidural or spinal reasonable?	Caution advised
Time from last dose to neuraxial block insertion	≥ 24 hours and confirm normal aPTT
Administration of drug while catheter in situ	Safety not established
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	≥ 1 hour
Remarks	Consider HITT if ≥ 4 days on heparin, and perform a platelet count

IV UFH therapeutic
Is epidural or spinal reasonable?	Caution advised
Time from last dose to neuraxial block insertion	≥ 4–6 hours and confirm normal aPTT
Administration of drug while catheter in situ	Caution advised ≥ 1 hour after block
Time from dose (while catheter in situ) to catheter removal	≥ 4–6 hours and confirm normal aPTT
Time from block/removal of catheter to next dose	≥ 1 hour
Remarks	Bloody or difficult needle placement may increase bleeding risk with subsequent IV heparin

IV heparin during surgery (5 000–10 000 U for vascular surgery)
Is epidural or spinal reasonable?	Yes
Time from last dose to neuraxial block insertion	Conduct ≥ 1 hour before heparinisation
Administration of drug while catheter in situ
Time from dose (while catheter in situ) to catheter removal	≥ 2–4 hours and confirm normal aPTT
Time from block/removal of catheter to next dose
Remarks	“Bloody tap” is not an absolute indication to cancel surgery

IV heparin (cardiopulmonary bypass)
Is epidural or spinal reasonable?	Not known
Time from last dose to neuraxial block insertion	Conduct ≥ 1 hour before heparinisation
Administration of drug while catheter in situ
Time from dose (while catheter in situ) to catheter removal	≥ 4-6 hours and confirm normal aPTT
Time from block/removal of catheter to next dose
Remarks	Certainly not routine practice; some place the epidural 12 hours preoperatively

SC LMWH prophylaxis once daily dose
Is epidural or spinal reasonable?	Yes
Time from last dose to neuraxial block insertion	≥ 12 hours
Administration of drug while catheter in situ	Can continue: 1st postop dose ≥ 12 hours after block; 2nd dose given ≥ 24 hours after 1st dose
Time from dose (while catheter in situ) to catheter removal	≥ 12 hours
Time from block/removal of catheter to next dose	≥ 4 hours
Remarks	Traumatic placement: no need to postpone surgery, but delay LMWH 24 hours

SC LMWH prophylaxis bd dose
Is epidural or spinal reasonable?	Caution advised, bd dose associated with increased risk of spinal haematoma
Time from last dose to neuraxial block insertion	≥ 12 hours
Administration of drug while catheter in situ	No
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	≥ 4 hours
Remarks	Traumatic placement: no need to postpone surgery, but delay LMWH 24 hours

SC LMWH therapeutic
Is epidural or spinal reasonable?	No
Time from last dose to neuraxial block insertion	If feasible, stop and wait ≥ 24 hours; consider checking antifactor Xa
Administration of drug while catheter in situ	No
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	≥ 4 hours
Remarks	Traumatic placement: no need to postpone surgery, but delay LMWH 24 hours

Warfarin prophylaxis
Is epidural or spinal reasonable?	Yes, if ≤ 24 hours after first dose
Time from last dose to neuraxial block insertion	Can do if ≤ 24 hours after first dose
Administration of drug while catheter in situ	Yes, monitor INR daily
Time from dose (while catheter in situ) to catheter removal	INR ≤ 1.5 and ≤ 48 hours after first dose If ≥ 3, cut warfarin
Time from block/removal of catheter to next dose	N/A
Remarks	Warfarin is usually started the evening before surgery

Warfarin established, therapeutic
Is epidural or spinal reasonable?	No
Time from last dose to neuraxial block insertion	N/A
Administration of drug while catheter in situ	N/A
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	N/A
Remarks	Can conduct if feasible to stop for 5 days; verify normal INR

Direct thrombin inhibitors (parenteral)
Is epidural or spinal reasonable?	No
Time from last dose to neuraxial block insertion	Not recommended
Administration of drug while catheter in situ	N/A
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	Not known
Remarks	Given IV, with an effect for up to 3 hours; no antagonist

Direct thrombin inhibitors (oral) dabigatran
Is epidural or spinal reasonable?	Carefully and individually considered; advised against in pts with CrC of ≤ 30 ml/min
Time from last dose to neuraxial block insertion	≥ 5 days
Administration of drug while catheter in situ	No
Time from dose (while catheter in situ) to catheter removal	N/A Unanticipated administration, wait 34–36 hours
Time from block/removal of catheter to next dose	≥ 6 hours
Remarks	Highly dependent on renal excretion

Anti-factor Xa inhibitors: fondaparinux
Is epidural or spinal reasonable?	Not known, limited clinical experience
Time from last dose to neuraxial block insertion	Not known
Administration of drug while catheter in situ	N/A
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	Avoid catheter
Remarks	AntiFxa effect for days

Direct oral anti-factor Xa agents (rivaroxaban^#, apixaban^##)
Is epidural or spinal reasonable?	Not known
Time from last dose to neuraxial block insertion	≥ 72 hours
Administration of drug while catheter in situ	No
Time from dose (while catheter in situ) to catheter removal	N/A Unanticipated administration, wait 22–26^# hours or 26–30^## hours
Time from block/removal of catheter to next dose	≥ 6 hours
Remarks	Newer drugs in this class: edoxaban and betrixaban

*Antiplatelets thienopyridines (clopidogrel and prasugrel)
Is epidural or spinal reasonable?	Most likely no
Time from last dose to neuraxial block insertion	If feasible, wait ≥ 5–7* days or ≥ 7–10** days
Administration of drug while catheter in situ	No
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	Stat if no LD given; if LD, ≥ 6 hours
Remarks	Given p.o.; inhibits ADP platelet aggregation

Antiplatelets ticagrelor
Is epidural or spinal reasonable?	Not known
Time from last dose to neuraxial block insertion	≥ 5–7 days
Administration of drug while catheter in situ	No
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	Stat if no LD given; if LD, ≥ 6 hours
Remarks	Antiplatelet effect within 30 minutes with maximum effect within 2 hours

Antiplatelets (GPIIb/ IIIa antagonists) abciximab⁺ eptifibatide⁺⁺ tirofiban⁺⁺
Is epidural or spinal reasonable?	No
Time from last dose to neuraxial block insertion	Waiting time of 4–8⁺⁺ hours or 24–48⁺ hours
Administration of drug while catheter in situ	No
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	N/A
Remarks	Contraindicated for 4 weeks after surgery; usually also on others (i.e. aspirin and LMWH)

Fibrinolysis and thrombolysis
Is epidural or spinal reasonable?	No
Time from last dose to neuraxial block insertion	≥ 48 hours and normal clotting studies including fibrinogen
Administration of drug while catheter in situ	No
Time from dose (while catheter in situ) to catheter removal	N/A
Time from block/removal of catheter to next dose	Remove and wait 10 days before starting Rx
Remarks	Effect may last 27 hours; also has an effect on platelets

ADP – adenosine diphosphate, aPTT – activated partial thromboplastin time, bd – twice daily, CrC – creatinine clearance, COX – cyclo-oxygenase, HITT – heparin-induced thrombocytopenia and thrombosis, INR – international normalised ratio, IV – intravenous, LD – loading dose, LMWH – low-molecular-weight heparin, N/A – not applicable, NSAIDs – nonsteroidal anti-inflammatory drugs, p.o – per os, Rx – treatment, SC – subcutaneous, Stat – immediately, UFH – unfractionated heparin

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South African Society of Anaesthesiologists (SASA) Guidelines for the Management of Acute Pain in Specific Scenarios 2022

Patient-Controlled Analgesia and Neuraxial Analgesia Techniques

Clinical guidelines on the use of patient-controlled analgesia

Chart 1: Proposed prescription chart

Neuraxial techniques

Drugs mentioned