Battlefield Analgesia

Abstract

This chapter begins with an overview of pain concepts, pain scoring, and analgesic options. It goes on to review current treatment suggestions for the ballistic casualty at each stage of their care. Finally, a series of appendices offer further information on the drugs, on patient controlled devices, and management of overdoses. Note: Medication regulatory issues vary around the world and are beyond the scope of this text. Therefore, these issues will not be discussed.

Appendices

Appendix I: Medication Review

These are not comprehensive instructions and no responsibility can be taken for doses suggested.

• Non Steroidal Anti Inflammatory Drugs (NSAIDs)

  • Diclofenac

  • Ibuprofen

  • Specific COX II Inhibitors.

• Opioids

  • Morphine

  • Pethidine

  • Fentanyl

  • Alfentanil

  • Remifentanil

  • Methadone

  • Hydromorphone

  • Weak Opioids

    • Codeine

    • Tramadol

    • Buprenorphine

• Other Analgesics

  • Ketamine

  • Paracetamol

  • Methoxyflurane

  • Entonox

• Peripheral Nerve Blocks

1.1 Non Steroidal Anti Inflammatory Drugs (Nsaids)

1.1.1 Mechanism

NSAIDs work by inhibiting the action of the enzyme cyclooxygenase. This prevents the production of a number of substances that are thought to produce pain as well as a number of other actions.

1.1.2 Effects

In addition to their analgesic and antipyretic actions NSAIDs are associated with a number of other effects.

1.1.2.1 Gastric Irritation

This can result in a spectrum of problems from mild pain to fatal hemorrhage. This side effect is thought to be reduced with the use of COX II inhibitors.

1.1.2.2 Inhibition of Coagulation

This is predominately through inhibition of platelet function although may be less with COX II inhibition.

1.1.2.3 Inhibition of Renal Function

Renal prostaglandin production may be reduced by NSAID administration. This can lead to a critical reduction in renal blood flow which in the presence of hypotension and hypovolaemia can lead to acute renal failure.

1.1.2.4 Inhibition of Bone Repair

This may be significant in long term use delaying fracture repair.

1.1.2.5 NSAID Sensitive Asthma

Up to 20% of asthmatics may experience a severe asthma attack on exposure to NSAIDs. Children appear to be relatively protected from this. These are associated with allergic rhinitis, nasal polyps, and middle aged asthma sufferers.

1.1.3 Agents

1.1.3.1 Diclofenac

Routes	Oral, intravenous and rectal
Doses	Adults 150 mg daily.

1.1.3.2 Ibuprofen

Of the most commonly used NSAIDs ibuprofen has the lowest rate of gastric side effects. This may be in part due to its having the weakest anti inflammatory properties – it does not follow that it necessarily has the weakest analgesic actions.

Routes	PO. peak analgesia being reached in 1–2 h.
Doses	Adult – 1,800 mg daily in 4–6 divided doses. Paeds – 5 mg/kg QDS

1.1.3.3 Ketorolac

Potent NSAID with advantage of having an intravenous formulation. Should be used with great caution in renal compromise. Doses range from 15–30 mg IV.

1.1.3.4 Specific COX II Inhibitors

These are thought to reduce the incidence of gastric complications and reductions in platelet function. Their use is also subject to “guidance” from a number of regulatory bodies and it is likely that their use will continue to change with time. Examples include celecoxib and paracoxib.

1.1.4 Opioids

1.1.4.1 Introduction

The term “opiate” refers to naturally occurring substances with morphine like properties whilst “opioid” includes the synthetic analgesics that act via the opioid receptors and are competitively antagonized by naloxone.

An important factor to consider when administering opioids is that individual dose requirements will vary between patients and even for the same patient on different occasions just as pain vaires. For this reason the best approach is to titrate the dose administered according to patient requirement. In this way one can achieve optimum analgesia with the minimum of side effects.

1.1.5 Strong Opioids

1.1.5.1 Morphine

The “gold standard” analgesic

1.1.5.1.1 Effects

• 1. Cental Nervous System

  • Analgesia

  • Sedation, followed by euphoria and then dysphoria with increasing dose

  • Meiosis, a result of Edinger – Westphal nucleus stimulation

  • Nause and Vomiting – the chemoreceptor trigger zone may be indirectly simulated but the vomiting center is not. In fact higher doses may inhibit the system so as to reduce nausea and vomiting.

  • Hallucinations in c. 3%

• 2. Respiratory System

  • Respiratory depression

  • Antitussive effect

  • Bronchospasm can occur, usually a result of histamine release.

• 3. Cardiovascular System

  • Histamine release is thought to result in a reduction in smooth muscle tone and a mild bradycardia.

• 4. Gastrointestinal

  • Gut sphincters contract and motility is reduced leading to constipation and possibly increased vomiting.

• 5. Genitourinary

  • Increased tone of the detrusor and sphincter muscles may precipitate urinary retention.

• 6. Musculoskeletal

  • Opioids can increase muscle rigidity. This appears to be more common following rapid intravenous administration rather than by other routes.

• 7. Skin

  • Puritis, most marked with epidural or intrathecal routes. Antihistamines may help although the role of histamine is uncertain.

• 8. Endocrine

  • ADH secretion is increased which may lead to impaired water excretion and hyponatraemia

Routes	Multiple routes possible, including intranasal. The subcutaneous route is not encouraged because of relatively low lipid solubility.
	Following intramuscular administration peak analgesia should be reached after c.10–30 min and may last 4 h. In the normal patient this is almost as as fast an onset as the intravenous route.
	Orally it has a 50% bioavailability.
	Morphine undergoes extensive biotransformation to active metabolites. Problems can be caused with renal failure causing reduced elimination.
Dose	The difficulty is that morphine the dose that can be given will depend upon the pain the patient experiences. There is no clear “upper limit.”
	An initial dose of 0.05–0.1 mg/kg iv or im should be used to start analgesia.
	In adults 2 mg iv every 5 min to titrate analgesia after an initial bolus.
	10 mg im can be repeated every 2 h although under appropriate supervision more than this may be required.

1.1.5.2 Pethidine

It is available as tablets and solution for injection. It is said to produce less biliary tract spasm than morphine although the clinical significance of this is often questioned.

Serious interaction is seen with monoamine oxidase inhibitors including coma, labile circulation, convulsions, and hyperpyrexia.

Anticholinergic effects such as a dry mouth and occasional tachycardia can occur.

It is inactivated in the liver to a number of metabolites including norpethedine which has half the analgesic activity of pethidine, a longer elimination half-life, an association with hallucinations and grand mal seizures, and effects not reversed by naloxone.

Routes	PO IV, IM
Dose	0.5–1 mg/kg, titrated to effect.

1.1.5.3 Fentanyl

A clear colorless intravenous solution also available in the form of transdermal patches, buccal and sublingual tablets, and a buccal “lollipop.”

An iontophoretic “PCA” patch is available.

It has negligible oral bioavailability which means that fentanyl has to be absorbed through the oral mucosa rather than “swallowed.”

One vital point to note when using this buccal route is that the lozenge has to “paint” the oral mucosa and not sit statically on one site if the drug is to be optimally absorbed. Tablet forms are now available for sublingual and buccal use that do not require this movement.

Fentanyl is said to release less histamine than morphine thus may not reduce blood pressure to the same degree (Fig. 20.2).

Fig. 20.2

Actiq^® oral transmucosal fentanyl applicator; the “Lollipop”

Dose	IV: 1 μ(mu)g/kg.
	Oral “lollipop”: Approximately 10–1 ratio with intravenous morphine (thus 800 μ(mu)g oral transmucosal fentanyl ≈ 8 mg iv morphine).10

1.1.5.4 Alfentanil

This is an opioid that is only really used for sedation and perioperative analgesia.

1.1.5.5 Remifentanil

It is a potent analgesic that will only be used perioperatively or for sedation.

1.1.5.6 Methadone

This is a synthetic opioid which is used in some parts of the world for the management of acute pain. It is thought to have a wide range of actions and not solely opioid in nature as it may have activity at NMDA receptors. It also has a long half-life.

1.1.5.7 Hydromorphone

Thought to have a swifter onset than morphine. Approximately four times more potent orally and eight times more potent via the parenteral route.

1.1.6 Weak Opioids

1.1.6.1 Codeine

It is approximately one sixth the potency of morphine. It is relatively more effective orally than parenterally.

Intravenous route tends to be avoided because of incidents of hypotension.

It has been suggested codeine is just a prodrug for morphine. However, approximately 9% of the UK population is poor metabolizers of codeine. This may often result in significantly reduced analgesia in this population. Conversely some people may be very good metabolizers and have an excessive response.11

Dose	Adult- 30–60 mg QDS; but more may be necessary.

1.1.6.2 Tramadol

Tramadol is described as a “weak” opioid and is indicated for the treatment of moderate to severe pain.

The effects are similar to those of morphine. It may make epilepsy more common in those that are susceptible to it.

It should not be given with monoamine oxidase inhibitors.

Dose	Up to 400 mg daily in divided doses.

1.1.6.3 Buprenorphine

Thought to be 30 times more potent than morphine. There have been suggestions that it is less likely to cause respiratory depression. However even high doses of naloxone have difficulty in antagonizing its actions.

Anecdotal reports suggest nausea and vomiting may be more common with buprenorphine than other opioids.

Routes	Sublingual, injection (im & iv)
Dose	Sublingual: 200–400 μg QDS

Intramuscular/slow intravenous: 300–600 μg QDS

1.1.7 Other Analgesics

1.1.7.1 Ketamine

Ketamine is a relatively unique drug that, like opioids, causes a range of actions from dysphoria and analgesia to death. However it is not an opioid but a phencyclidine derivative.

There is a belief that the stereoselective isomer has a better side effect profile than the racemic mixture but it is the latter that one finds more often.

The traditional use of ketamine was limited to use as an anesthetic agent in the hemodynamically unstable trauma patient. The US Army has been able to frequently utilize subanesthetic doses of ketamine in low rate continuous infusions and PCA combinations in perioperative and acute pain management. Advantages to the use of ketamine in this context have been a reduction in opioids required to reach a given level of pain relief, decreased risk of respiratory depression, reduction of the development of opioid tolerance, prevention of opioid-induced hyperalgesia, and although controversial, reduction of risk of chronic pain.12

1.1.8 Effects

1.1.8.1 CNS

The anesthesia produced is typically described as “dissociative anesthesia.”

Limb movement may occur as may groaning. These do not necessarily indicate a light anesthetic.

Sedation occurs in sub-anesthetic doses in common with analgesia.

Dreaming and hallucinations occur especially on emergence and during sedation. These can be vivid and worrying and are more common in adults than children. They may be reduced with concomitant administration of opiates or benzodiazepines.

Consequently the issue of ketamine use in the head injured patient is being reviewed.

There can be preservation of corneal and light reflexes together with slow nystagmic gaze.

1.1.8.2 Respiratory System

Respiratory function is relatively well preserved as are airway reflexes. Ketamine is acts as a bronchodilatator.

An increase in salivary and tracheobronchial secretions occurs and this may be problematic.

1.1.8.3 Cardiovascular

Ketamine is a potent sympathomimetic. This action tends to mask its myocardial depressant and venodilatation actions, certainly on initial dosage. Myocardial depression is less with ketamine than it is with other intravenous anesthetic agents.

Routes	Intravenous and intramuscular routes remain the military routes of choice at present. Intranasal route may have some uses. Intramuscular Ketamine has a peak plasma level of about 20 min.
Doses	Analgesia and sedation is usually to be found using subanesthetic doses; low infusion rates for analgesia range from 0.5–2mcg/kg/min; infusion for sedation for painful procedures ranging from 5–10mcg/kg/min; PCA mixtures most commonly 1 mg morphine/1 mg ketamine; 10–20 mg bolus aliquots titrated for effect and repeated as required.

1.1.8.4 Paracetamol

In common with many other NSAIDS paracetamol is freely available over the counter either alone or in combination with a number of other drugs. For this reason, as mentioned above, there is a real possibility of overdose, either deliberate or accidental. Commonly described as having “synergy” with other analgesics with approximate 20% opioid-sparing analgesic properties.

1.1.9 Effects

1.1.9.1 CNS

The exact site of paracetamol’s action is still under debate but as well as being an analgesic it also has good antipyretic properties.

1.1.9.2 GI

Unlike traditional NSAIDs paracetamol is not thought to have an irritant effect on the gastric mucosa.

1.1.9.3 GU

In overdose there is a risk of renal tubular necrosis.

Table 11

1.1.9.4 Methoxyflurane

This is an inhaled anesthetic vapor that in low doses gives good pain relief. It is in use with the Australian and New Zealand Defence Forces. However there are side effects and complications associated with it that make its use in British forces unlikely.13

1.1.9.5 Entonox

This is mixture of oxygen and nitrous oxide. Again it requires a degree of coordination to allow inhalation. It requires a relatively bulky apparatus to provide it. There are also practical issues surrounding its use and storage that make it unattractive for use in the prehospital environment. Below − 6°C, the pseudocritical temperature of entonox, the mixture undergoes lamination and nitrous oxide enters the liquid phase. Thus initially oxygen alone is delivered and then only nitrous oxide. It should also be avoided in patients with bowel obstruction, pneumothorax, sinus, and middle ear disease.

1.1.9.6 Peripheral Nerve Blocks

In depth discussion on the use of peripheral nerve blocks is outside the scope of this chapter.

Limb blocks are the most common blocks used. They can be either as “single shot” injections or as infusions. They may be done “blind” or guided using peripheral nerve stimulators or even ultrasound.

Appendix II: Patient Controlled Analgesia

2.1 Introduction

As the name suggests, this is a technique by which the patient is able to control the administration of their analgesia.

The current British military device is the Baxter “Wristwatch” PCA. US forces have utilized several different PCA pumps (most commonly the Sorenson “Ambit”) which have also been utilized for continuous peripheral nerve blockade. There has been effort to switch to a separate, color-coded, standardized pump for each use to avoid confusion.

Typically morphine 2 mg/ml is the solution used with this system. The addition of an antiemetic to this solution is not encouraged.

This system does not provide a one-stop solution to the problems of analgesia for all patients, and it does not transfer all responsibility for analgesia to the patient but it may help reduce nursing workload. However, the patient does need to be monitored by the ward staff to confirm efficacy, and watch for unwanted side effects from the morphine. To aid this it is normal practice for a suitable protocol to be employed on the wards and an example of this is given below.

The fentanyl iontophoretic patch PCA, “Ionsys” does exist but at present there are no plans for its widespread use within the military system.

2.2 PCA Protocol

Patient suitability is determined by an anesthetist or the acute pain team in conjunction with ward staff.

The PCA must be prescribed on a suitable drug prescription chart. This does not prevent the prescription of other analgesics although care should be taken with alternative medication that may augment unwanted side effects of the morphine.

Regular recordings of pulse, blood pressure, respiratory rate, pain, and sedation (see below) are required. Typical timings are:

• Recovery – 5 min. To include S_pO₂ until stable.

• Ward – hourly for 4 h and then 4 hourly.

However, if the PCA was started on the ward then as for recovery for the first hour.

2.3 Pain and Sedation Score

Tables 20.2 and 20.3.

Table 20.2 Pain score

Table 20.3 Sedation Ssore

Appendix III: Oxygen Administration Protocol

Patients who have one of the following signs should be given supplementary oxygen:

• S_pO₂ < 95% on air

• Sedation score of 3 (see pca protocol for scoring scale)

• Respiratory rate < 9/min

Oxygen should be started at 4l/min via a mask immediately.

Regular recordings of pulse rate, respiratory rate, blood pressure, S_pO₂, and sedation should be initiated.

Refer to the Opiate Overdose Protocol if this is thought to be the origin of the respiratory depression.

The medical staff should be informed as soon as possible.

Ensure the location of the resuscitation equipment is confirmed.

Appendix IV: Protocol Opiate Overdose

Typical signs are:

• Respiratory rate < 9

• Sedation score of 3 (severely sedated, difficult to rouse)

• Reduced S_pO₂

Prompt intervention is required to prevent a potentially threatening event occurring.

If opiate overdose is suspected:

• Give oxygen, according to the Oxygen Administration. Protocol

• Give Naloxone 0.4 mg iv bolus. This may need to be repeated after 10–15 min.

• Inform the medical staff as soon as possible.

Appendix V: Paracetamol Overdose

As little as 5 g of paracetamol taken in a 24 h period may lead to severe hepatic damage. This damage is maximal after 3–4 days but initial symptoms may be sufficiently mild as to not cause undue concern.

Actual plasma paracetamol levels may be difficult to obtain in field conditions. However, if 150 mg/kg has been taken with the last hour administration of activated charcoal is suggested. Antidotes such as acetylcysteine and methionine may protect the liver if given within 12 h of ingestions, although the former may be protective up to 24 h after ingestion.

Appendix VI: UK : US Drug Names

Often US generic drug names will be different to UK names. Almost always the Brand name will be different and these are used more often in the US than the UK.

This list is not exhaustive (Table 20.4).

Table 20.4 UK: US drug names