Local anesthesia - Lignocaine hydrochloride 1% (10mg/ml), 2ml, 5ml, and 10ml ampoules for injection Lignocaine hydrochloride 2% (20mg/ml), 2ml and 5ml ampoules for injection. Effects Lignocaine blocks sodium channels, reducing the conduction rate and amplitude of ne rve electrical impulses. Indications - Ventricular arrhythmias - Painful localized patholog y - Local anesthesia for painful procedures. Dose - Ventricular arrhythmias: 100mg by slow intravenous bolus (dose may be reduced in smaller patients) - Local anesthesia: see notes below - Children (local anest hesia): 3mg/kg. Contraindications - Anti-arrhythmic therapy: sino-atrial disorders, atrio-v entricular block. - Local analgesia: hypovolaemia, complete heart block. - Solutions with a drenaline: see notes below. Side-effects - These are rare with single applications of topic al lignocaine. - Inebriation and lightheadedness followed by sedation, circumoral paraesthesia, and twitching; convulsions in severe cases. Convulsions and cardiovascular collapse on intravenous administration. Notes 0.5% lignocain e is available for local anesthetic use. It is NOT recom- mended in the pre-hospital enviro nment. A MAXIMUM safe lignocaine dose for an average adult is 20ml of 1% (200mg) or equivalent vol ume of higher concentration solution. This dose can be increased if lignocaine is given wit h a vasoconstrictor such as adrenaline. Use of lignocaine with adrenaline may cause gangren e if injected into digits or appendages and is NOT RECOMMENDED in pre-hospital care. DRUGS1 333 Magnesium Description Administered as magnesium sulfate. Presentation Magnesium sulfate 50% \210\227, 2ml (1g) and 10ml (5g) ampoules, 10ml pre- filled syringe. Effects Precise mecha nism not known; effective in acute severe asthma. Indications - Acute severe asthma - Ventr icular tachycardia - Torsade de pointes. Dose - Asthma: 1.2 \200\2232g iv over 20 minutes - VT, torsade de pointes, and refractory VF: 8mmoles (4ml or 2g) over 30 minutes (followed by infusion after arrival in hospital). Contraindications None. Side-effects Symptoms of hypermagnesaemia: nausea, vomiting, flushi ng, hypotension, arrhythmias, respiratory depression, drowsiness, and confusion. Notes The dose of magnesium given above for the treatment of asthma should only be given ONCE to avoid symptomatic hypermagnesaemia. \210\227 1ml of 50% magnesium contains 2mmol magnesium. 20% magnesium sulfate is also avai lable (0.8mmol/ml). CHAPTER 4 Formulary 334 Methionine Description Paracetamol antidote. Presentation 250mg tablets. Indications The fi rst-line treatment for paracetamol overdose is N-acetylcysteine after arrival in hospital a nd within four hours of the overdose. Methionine is only indicated (and need only be carrie d) in areas in which prompt evacuation is likely to be impossible. Dose - Adult and child o ver 6: 2.5g initially followed by three further doses of 2.5g every 4 hours orally. Child under 6: 1g initially followed by three further doses of 1g orally. Contraindications Since it is given orally, methionine is ineffective in patients who are vomiting. Side-eff ects Nausea, vomiting, drowsiness, irritability. DRUGS1 335 Metoclopramide Description Prokinetic antiemetic. Presentation 5mg/ml, 2ml (10mg) ampoule for injection. Effects Antiemesis by central antagonism of dopamine. Cholinergic effects on the gut includ e increased gastric emptying, pyloric sphincter relaxation, increased lower oesophageal sph incter tone, and stimulation of peristalsis. Indications - Nausea and vomiting - Adjunct treatment with opiate analgesics. Dose 10mg by iv injection (may also be given im). Contraindications Not to be used in patients UNDER 20 YEARS OLD due to an increased risk of acute dystonic reactions. Side-effects Extrapyramidal effects (dystonia). Other side-effects are rare. Notes The treatment for extrapyramidal effects is benztropine 1 \200\2232mg by iv or im inj ection or procyclidine 5 \200\22310mg by im or iv injection. Management of these symptoms s hould take place in hospital. CHAPTER 4 Formulary 336 Midazolam Description Sedative hypnotic benzodiazepine. Presentation - (Midazolam hydrochloride 1mg/ml, 50ml vial) - Midazolam hydrochloride 2mg/ml , 2ml and 5ml ampoules - Midazolam hydrochloride 5mg/ml, 2ml, 5ml, 10ml, and 18ml ampoules. Effects Acts through membrane GABA receptors to stabilize membranes, primarily in the CNS, and reduce depolarization. Indications - Sedation and amnesia for clinical procedures - Co-administration with ketamin e to reduce emergence phenomena (not required in children). Dose - 2 \200\2232.5mg (0.5 \200\2231mg in the elderly) by slow iv injection, increasing in increments of 1mg (0.5 \200\2231mg in elderly). Children: (by SLOW iv injection) 6 months \200\2235 yrs, initially 50 \200\223100ug/kg; 6 \200\22312 yrs, 25 \200\22350ug/kg. Further increments are given to effect. Contraindications Severe respiratory depression, acute pulmonary insufficiency, myasthenia gravis. Side-effects - Respiratory depression and arrest (overdosage or too rapid administration) Drowsiness, confusion, ataxia, amnesia, headache, vertigo. - Excitement and aggression (mor e common in children and the elderly). Notes Midazolam can also be given by im or rectal routes. DRUGS1 337 Morphine Description An opiate analgesic. Presentation - Morphine sulfate 10mg/ml, 15mg/ml, 20mg/ml, and 30mg/ml \200\2241 and 2ml ampoules Morphine sulfate 10mg/ml \200\2241ml pre-filled syringe - Morphine sulfate 1mg/ml \200\2241 0ml pre-filled syringe - Larger-volume vials are available but are intended for iv infusion preparation. Effects Binds to opiate receptors resulting in analgesia, euphoria, and respiratory depress ion. Indications Acute severe pain Dose - Morphine should be given by iv injection in small aliquots titrated to effect. An initial dose of 5mg is appropriate for an adult male, 2mg for smaller or older p atients. Doses of up to 30mg may be required in fit young men with severe pain. Children: up to 1 month, 37.5 \200\22375ug/kg; 1 \200\22312 months, 50 \200\223100ug/kg; 1 \200\2235 years, 1 \200\2232mg; 6 \200\22312 years, 2 \200\2235mg. All by iv injection. Contraindications Acute respiratory depression. Side-effects Nausea and vomiting, drowsiness, respiratory depression, hypotension, hallucin ations. Acute allergic reactions. Notes The labeling on ampoules of proprietary morphine is identical except for the concentr ation. It is imperative that this is carefully checked if dosing errors are to be avoided. Morphine should always be adminis- tered in a concentration of 1mg in 1ml (10mg in 10ml). An antiemetic should be administered with any iv opiate, however the use of Cyclimorph (morphine/cyclizine) is not recommended . Naloxone and equipment for mechanical ventilatory support MUST be available when morphine (or any other opiate) is administered. Morphine has a duration of action of about 2 hours. CHAPTER 4 Formulary 338 Naloxone Description A competitive opiate antagonist. Presentation - 400ug/ml, 1ml ampoule - 400ug/ml 1ml, 2ml, and 5ml pre-filled syringe - 1mg/ ml, 2ml pre-filled syringe. Effects Reversal of opioid effects. Indications - Reversal of therapeutic overdose of opiates - Treatment of opiate poisoning ( recreational overdose) - Treatment of unexplained loss/reduction of consciousness. Dose - 0.4mg(400ug) \200\2232mg repeated at intervals, as required, to a maximum of 10mg If naloxone is given to exclude opiates as a cause of loss of consciousness, a dose of 10mg should be given Children: intravenous 10ug/kg, subsequent dose of 100ug/kg if no response. Contraindications Caution in patients who are physically dependent on opiates; will precipi - tate pain in patients given opiate for analgesia. Side-effects Nausea and vomiting, tachycardia. Notes Naloxone is short-acting. As a result, when long-acting opiates are being reversed, r epeated doses may be needed. Drug abusers may leave the scene after a first dose only to co llapse as the naloxone wears off. In order to reduce the likelihood off this, either the op iate can be reversed only enough to ensure adequacy of respiration before arrival in hospit al, or a similar dose to the intravenous one given above may be given INTRAMUSCULARLY, in a ddition. This page intentionally left blank CHAPTER 4 Formulary 340 Nitrous oxide/oxygen 50:50 (Entonox) Description 50:50 mixture of oxygen and nitrous oxide (N2O). Presentation Various sizes of blue cylinder with a white and blue mantle. Self admin is- tered with override valve. Effects Analgesia without loss of consciousness. Indications - Analgesia for moderate pain in fully conscious individuals - Analgesia for sh ort, painful procedures Dose Titrate to effect. Usually self administered using a demand valve. May be overridden b y medical staff. Contraindications Contraindicated in patients in whom an air-filled cavity exists into whic h nitrous oxide can diffuse. These conditions include pneumothorax (so contraindicated in s ignificant chest injury), the \200\230bends \200\231 (so contraindicated in patients follo wing diving), and open head injuries. Side-effects See above Notes At temperatures less than \200\2237 C, nitrous oxide/oxygen mixtures will separate. This may lead to inhalation of pure oxygen with no analgesic effect, followed by pure nitr ous oxide leading to hypoxia. A few shakes of the cylinder will have no effect on this sepa ration. Entonox MUST be kept above \200\2237oC, even if this means transferring it to your vehicle immediately before departure. DRUGS1 341 Ondansetron Description Specific 5HT3 antagonist. Presentation - 4mg and 8mg tablets - Onda nsetron hydrochloride 2mg/ml, 2ml and 4ml ampoules for slow iv injection. Effects Blocks 5HT3 receptors in the gastrointestinal tract and CNS. Indications Nausea and vomiting. Dose - 4mg orally - 4 \200\2238mg by slow iv injection - Children: 100ug/kg by slow iv inje ction. Contraindications Caution in pregnancy and breastfeeding. Side-effects Sensation of warmth or flushing, transient visual disturbance and dizzi- ness. (Rarely, fits, chest pain arrhythmias, hypotension, and bradycardia.) Notes May also be given orally or by im injection. CHAPTER 4 Formulary 342 Oxygen Description Invisible odorless gaseous element. Presentation Black cylinders with a white collar and neck. Effects Increases alveolar oxygen tension, decreases work of breathing, and improves arteri al oxygen tension. Indications Hypoxia (for example, due to trauma, chronic obstructive pulmonary disease (COP D), asthma, or pulmonary embolism). Dose High flow (12 \200\22315l/min) by Hudson mask with rebreathing bag for trauma and othe r causes except COPD, (in which case, low flow 24 \200\22328% by fixed or variable rate mas k). Contraindications High-flow oxygen is contraindicated in patients with COPD and oxygen, in patients with paraquat poisoning. Side-effects Exacerbation or precipitation of respiratory failure if given in high dose to patients with elevated PaCO2 dependent on hypoxic drive. DRUGS1 343 Sizes and capacities of conventional oxygen cylinders Size Capacity (litres) Duration at 15l/min C 170 11 D 340 22 E 680 45 F 1360 90 G 3400 225 Ambulance services are increasingly carrying the CD size lightweight cylinder which contain s 460 litres of oxygen, and lasts 30min with a deliv- ery rate of 15 litres/min. CHAPTER 4 Formulary 344 Pancuronium See pp.385 \200\2236. DRUGS1 345 Paracetamol Description A simple analgesic with weak anti-inflammatory properties. Presentation - Tablets: 500mg (also as dispersible paracetamol) - Pediatric suspension: 120 mg/5ml \210\227 - Suppositories: 60mg, 125mg, 250mg, and 500mg. Effects Inhibits brain prostaglandin synthesis. Indications - Mild to moderate pain, especially in children (aspirin contraindicated) - Pyr exia Dose Adults: 500mg \200\2231g orally, maximum 4g in 24 hours orally or by suppository Child ren: - Orally: Under 3 months \200\22410mg/kg (5mg/kg if jaundiced); on doctor \200\231s advice only 3 months \200\2231 year \200\22460 \200\223120mg - 1 \200\2235 years \200\224120 \200\22325 0mg - 6 \200\22312 years \200\224250 \200\223500mg. These doses may be repeated every 4 \200\2236 hours, maximum 4 doses in 24 hours - By suppo sitory: 1 \200\2235 years \200\224125 \200\223250mg - 6 \200\22312 years \200\224250 \200\223500mg - Over 12 years \200\224500mg \200\2231g. Contraindications None for single dose in acute situation, but check with regard to patient \200\231s 24-hour total dose, especially with respect to compound analgesics containing pa racetamol. Side-effects No significant acute side-effects. Notes Paracetamol is extremely toxic in overdose. \210\227 Pediatric tablets and adult suspension (250mg/ml) are also available. CHAPTER 4 Formulary 346 Pethidine Description Synthetic opioid with a shorter duration of action than morphine. Presentation - 50mg/ml in 1ml and 2ml ampoules for injection - 10mg/ml in 5ml and 10ml ampo ules - Oral pethidine is not suitable for pre-hospital use. Effects - Analgesia - Obstetric analgesia (pethidine does not delay labor) - Atropine-like effects \200\224blurred vision, dry mouth. Indications - Moderate pain - Obstetric pain. Dose - 20 \200\22350mg by slow iv injection - 50 \200\223100mg sc or im for obstetric analg esia. Contraindications - Patients taking monoamine oxidase inhibitors - Acute respiratory depres sion - Care in head injury. Side-effects - See morphine - There is no evidence to suggest that pethidine has less effec t than morphine on the sphincter of Oddi. Notes - Onset within 10 minutes, duration of action 1 \200\2232 hours - Pethidine is associ ated with a greater risk of hypotension because of its alpha blockade, it is NOT RECOMMENDE D for pre-hospital use. DRUGS1 347 Prilocaine See p.392. Propofol See p.382. Rocuronium See p.385. CHAPTER 4 Formulary 348 Salbutamol Description B2 adrenergic receptor agonist. Presentation - Nebulizer solution 1m g/ml 2.5ml (2.5mg) nebules, 2mg/ml 2.5 ml (5mg) nebules Metered dose inhaler 100 g per puff. Effects Relaxation of smooth muscle resulting in bronchodilatation. Indications Acute asthma. Dose - 5mg as nebulized solution - Child over 18 months \200\2242.5mg as nebulized solution (under 18 months, 1.25 \200\2232.5 mg as nebulized solution). - Doses may be repeated if necessary. Contraindications None in acute use for severe asthma. Side-effects Tachycardia, fine tremor, headache, peripheral dilatation, palpitation, and ar rhythmias. Notes If a nebulizer is not available, salbutamol may be given by metered dose inhaler (MDI ) via a spacer device. DRUGS1 349 Suxamethonium See p.384. CHAPTER 4 Formulary 350 Syntocinon (oxytocin) Description An oxytocic. Presentation - 5 units/ml, 1ml ampoule - 10 units/ml, 1ml ampoule. Effects Contracts uterine muscle. Indications Control of excessive uterine bleeding following delivery. Dose 5 \200\22310 units by intravenous injection. Contraindications Caution in patients with predisposition to uterine rupture. Side-effects - Rapid IV injection may cause transient hypotension - Nausea, vomiting, arrhy thmias. DRUGS1 351 Tenecteplase Description Fibrinolytic. Presentation Powder for reconstitution, 40mg (8000 units), 50mg (10,000 units) Both with pr e-filled syringe of water for injections. Effects Acts as a thrombolytic by activating plasminogen to form plasmin which degrades fib rin and breaks up thrombi. Indications Acute myocardial infarction. Dose 500 \200\223600mcg/kg (maximum 50mg) by iv injection over 10 seconds. Contraindications - Recent hemorrhage, trauma, or surgery (including dental extraction) - C oagulation defects - History of cerebrovascular disease - Recent symptoms of peptic ulcerat ion - Heavy vaginal bleeding - Severe hypertension - Active pulmonary disease with cavitati on - Acute pancreatitis/severe liver disease - Oesophageal varices. Side-effects - Nausea and vomiting - Bleeding - Reperfusion arrhythmias - Hypotension. CHAPTER 4 Formulary 352 Thiopentone See p.383. DRUGS1 353 Tramadol Description A synthetic opiate with additional actions (see below). It is a non-se lective OP1 and OP3 receptor agonist, acting mainly at the OP1 receptor. Presentation Trama dol hydrochloride 50mg/ml, 2ml ampoule. Effects Tramadol has opioid and non-opioid mechanis ms of pain relief. It inhibits reuptake of 5HT and noradrenaline. It inhibits noradrenaline uptake and enhances serotonin release. Indications Moderate to severe pain. Dose 50 \200 \223100mg IV every 4 \200\2236 hours. Contraindications See morphine, also epilepsy (p.146) Side-effects - Tramadol is claimed to be less likely to cause constipation and respiratory depression than other opioids Confusion, fits, and anaphylaxis - Nausea. Pre-hospital use of tramadol is not recommended. CHAPTER 4 Formulary 354 Vecuronium See pp.385 \200\2236. This page intentionally left blank CHAPTER 4 Formulary 356 Pediatric doses Adrenaline INTRAMUSCULAR for anaphylaxis - Under 6 months: 50 g, 0.05ml, 1 in 1000 - 6 mon ths \200\2236 years: 120 g, 0.12ml, 1 in 1000 - 6 \200\22312 years: 250 g, 0.25ml, 1 in 1 000 - 12 years and over: 500 g, 0.5ml, 1 in 1000 Atropine 20 g/kg, maximum 600 g Benzyl penicillin - Under 1: 300mg - 1 \200\2239 years: 600mg - 10 years and over: adult dose Chl orpheniramine - 1 month \200\2231 year: 250 g/kg - 1 \200\22312 years: 200 g/kg or 1 \200\2235 years: 2.5 \200\2235mg - 6 \200\22312 years: 5 \200\22310mg Diazepam - Rectal \200\224children over 10kg, 500 g/kg, maximum 20mg - Intravenous \200\224300 \200\223400 g/kg or 1mg per year of age Glucagon - Under 8 years (or under 25kg): 500 g - Over 8 years (or over 25kg): 1mg Hydrocortisone - Up to 1 year: 25mg - 1 \200\2235 years: 50mg - 6 \200 \22312 years: 100mg pediatric DOSES1 357 Ibuprofen - 3 \200\2236 months: 50mg (body weight over 5kg) - 6 months \200\2231 year: 50mg - 1 \200\2233 years: 100mg - 4 \200\2236 years: 150mg - 7 \200\2239 years: 200mg - 10 \200 \22312 years: 300mg Ketamine As adult doses, by weight (See p.331) Lignocaine Local anesthe sia, 3mg/kg Methionine Child over six: 2.5g initially, followed by 3 further doses of 2.5g every 4 hours Child under six: 1g initially, followed by 3 further doses of 1g every 4 hour s Midazolam (iv) - 6 months \200\2235 years: 50 \200\223100 g/kg initially - 6 \200\22312 years: 25 \200\22350 g/kg, further increments as required Morphine - Up to 1 month: 37.5 \200\22375 g/kg - 1 \200\22312 months: 50 \200\223100 g/kg - 1 \200\2235 years: 1 \200 \2232mg - 6 \200\22312 years: 2 \200\2235mg Naloxone 10 g/kg, subsequent dose of 100 g/kg if no response Paracetamol Orally - Under 3 months: 10mg/kg (5mg/kg if jaundiced), on doct or \200\231s advice only 3 months \200\2231 year: 60 \200\223120mg - 1 \200\2235 years: 120 \200\223250mg - 6 \200 \22312 years: 250 \200\223500mg These doses may be repeated every 4 \200\2236 hours, maximu m 4 doses in 24 hours Suppository - 1 \200\2235 years: 125 \200\223250mg - 6 \200\22312 yea rs: 250 \200\223500mg - Over 12 years: repeat dosing as above CHAPTER 4 Formulary 358 Salbutamol (Over 18 months: 2.5mg as nebulized solution) under 18 months: 1.25 \200\2232.5m g as nebulized solution Chapter 5 359 Analgesia and anesthesia Overview 360 Routes of administration 362 Useful analgesics: opioids 364 Diamorphine 367 Fe ntanyl 368 Morphine 369 Pethidine 370 Tramadol 372 Naloxone 373 Treatment of opiate overdos age 374 Antiemetics 375 Other analgesics 376 Anesthesia 380 CHAPTER 5 Analgesia and anesthesia 360 Overview Pain management is an essential part of effective pre-hospital care, particularly in traumatic injury and acute myocardial infarction. In road traffic collisions, analgesia helps facilitate extrication as well as realign- ment and splintage of fractures. The provi sion of analgesia should be regarded as normal practice that requires careful patient asses sment, appropriate analgesic selection, and careful monitoring of the patient for both clin ical effectiveness and adverse reactions. The method and choice of analgesia will vary depe nding on the skills of the practitioner. The International Association for the Study of Pain defines pain as \200\230an unpleasant sensory and emotional experience associated with actual or potential tissue damage or descr ibed in terms of such damage \200\231. Physical trauma results in the patient experiencing both physiological and psycho- logical discomfort which is subject to individual variation and manifesta- tions. The sequence of both physiological and psychological events may resul t in an increase in morbidity. Inadequate pain relief will result in a reactionary stress r esponse which may include hyperglycaemia, increased levels of ADH and catecholamines, enhan ced coagulation, and immuno- suppression. The clinical manifestations may include tachycard ia, hypoxia, hypertension, deep venous thrombosis and pulmonary embolism, fluid retention, and infection. This page intentionally left blank CHAPTER 5 Analgesia and anesthesia 362 Routes of administration Effective analgesia should be given as quickly and safely as possi ble. Known drug allergies and current medication should, if possible, be identified and any potential side-effects considered prior to drug administration. The routes available for a nalgesic administration are: - Oral - Nasal - Sublingual - Rectal - Topical - Subcutaneous - Intramuscular - Intravenous - Intraosseous - Inhalation. Oral The oral route has no use for the relief of pain following significant trauma where th e onset is slow, nausea and vomiting common, and gastrointestinal motility decreased. In ad dition, some patients will have an altered level of consciousness. Simple oral analgesics m ay be prescribed for lesser trauma such as minor soft tissue injuries. Nasal Some lipid soluble opioids, including Fentanyl, may be given via the intranasal route with fairly rapid systemic effects. This route is currently used by some emergency departm ents and its pre-hospital use is being evaluated. Sublingual In sublingual administration, absorption bypasses the portal system leading to a rapid response and a more predictable efficacy. This route is being currently being evalua ted (for example, fentanyl lollipops.) Rectal Unpredictable absorption, slow drug metabolism, and practical issues make this route unsuitable for the trauma patient and reduce its relevance in pre-hospital care. Topical This is not a route used in acute pain management. Analgesic patches are used for c hronic pain relief. Subcutaneous An unpredictable response, especially in the shocked patient where cutaneous v asoconstriction will reduce absorption, makes this route unsuitable for acute use in pre-ho spital care. ROUTES OF ADMINISTRATION1 363 Intramuscular As for the subcutaneous route, slow absorption and an unpredictable response makes the intramuscular route dangerous, especially if, due to poor response, additional an algesia is subsequently given, risking a depot effect. Once the circulation is restored, ra pid absorption may lead to overdosage with catastrophic consequences. Intramuscular injecti ons should also be avoided in patients who are taking anticoagulants. Intravenous The ability to gain intravenous access is a prerequisite and not an option for all pre-hospital personnel. It allows delivery of analgesia promptly, predictably, and in a controlled way, and is the preferred route for the patient with significant trauma. Intraosseous This is an effective route for drug and fluid administration in children, comm only using the tibial metaphysis. Adult intraosseous access using selected long bone metaph yseal sites or the sternum is becoming estab- lished in cases in which intravenous access c annot be obtained. Absorption is almost as quick as the intravenous route. Infusion is faci litated by bolus injection using a syringe and three-way tap. Inhalation Entonox is a potent analgesic gas consisting of a 50/50 mixture of nitrous oxide and oxygen. Administration relies on the co-operation and physical capability of the patie nt to inhale from a well-fitting facemask or mouthpiece. It provides effective short-term a nalgesia. Being more soluble than nitrogen in plasma, it diffuses into air-filled cavities and will r esult in deterioration in patients with air in the cranial vault, pneumothorax, and bowel o bstruction. Decompression sickness is an absolute contraindication for its use. Route of choice For most medical and paramedical personnel working in pre-hospital care, mo rphine given by the intravenous route is the gold standard. Ten milligrams of morphine made up with sterile water to ten milliliters and titrated to effect is a safe and effective wa y of providing pre-hospital analgesia. It must be remembered that the dose of opiate requir ed to achieve comparable levels of analgesia may vary as much as ten times between individu al patients. CHAPTER 5 Analgesia and anesthesia 364 Useful analgesics: opioids An opioid is a naturally occurring or synthetic drug which will bind to and stimulate an opioid receptor. An opiate is a naturally occurring drug structura lly related to opium alkaloids. There are several different types of opioid receptors \200 \224OP1 (formerly m ), OP2 (formerly kappa), and OP3 (formerly delta). Opioids ma y function as receptor agonists, partial agonists, and antagonists. - Agonists Have affinity and intrinsic activity - Bind and stimulate opioid receptors - Produce a dose -related effect - Have differing efficacy. Partial agonists Bind and stimulate opioid receptors - Are limited by a ceiling action (beyond a certain dos e, further administration has no additional effect). Antagonists Bind to opioid receptors and produce no clinical effect. Examples of specific drug actions and their receptor activity include: - Morphine Pure agonist - Acts at OP1 receptor \200\224stimulant - High efficacy. Naloxone Antagonist - Acts at OP1 and OP2 receptors - Reverses respiratory depression and analgesic affects - Short half life compared with morphine/diamorphine. USEFUL ANALGESICS: OPIOIDS1 365 Table 5.1 Opioid receptor activity in relation to drug administration OP1 OP2 OP3 Analgesia Respiratory depression Miosis Nausea Bradycardia Analgesia Miosis Dysphoria Anti-analgesic Dysphoria Mydriasis Respiratory stimulation Tachycardia Effects at receptor site Agonist Morphine Diamorphine Pethidine Partial agonist Nalbuphine Antagonists Naloxone Nalbuphine CHAPTER 5 Analgesia and anesthesia 366 Side-effects and contraindications Opioids acting at the OP1 opioid receptors have similar side-effects in equianalgesic dosage. In all cases, hypovolaemia increases the risk of adve rse events. Potential problems include: Respiratory depression - Decreased central ventilatory response to hypercapnia and hypoxia - Depression of the cough reflex - Bronchospasm - Reduction of pain-driven sympathetic acti vity with improved cardiovascular stability Bradycardia and hypotension (in overdosage) - Sedation, euphoria, and anxiolysis - Miosis - Decreased gut motility - Nausea and vomiting. Contraindications Opioids are contraindicated in the following circumstances: - Pre-existin g respiratory depression (rate less than 10 breaths per minute). Raised intracranial pressure in non-ventilated patients where respiratory depression may lead to hypercapnia and worsening cerebral oedema. Status asthmaticus in non-ventilated patients. - Where appropriate drugs and equipment for the management of overdosage are not available. Opioids should be administered with caution in the presence of hypo- volaema, altered level of consciousness, and liver and renal disease. Carefully titrated opiate analgesia may improve respiratory function in patients with rib f ractures or chronic obstructive pulmonary disease complicated by trauma. Analgesia should n ot be withheld in head-injured patients. However, care must be taken to avoid CO2 retention which can occur with respiratory depression. Individual opioids with the same mode of receptor activity will produce similar side-effect s in equianalgesic doses. With each and every opioid, the drug should be administered slowl y whilst observing the clinical response. USEFUL ANALGESICS: OPIOIDS1 367 Diamorphine Description Opiate analgesic (heroin hydrochloride). Presentation Powder for reconstitution, 5mg and 10mg ampoules (larger dose ampoules are ava ilable) Onset is more rapid than morphine. Effects - Binds to opiate receptors resulting in analgesia, euphoria, and respiratory depression. Decreases pre- and after-load (central mechanism) and increases force of ventricular contraction and ejection fraction Indications - Acute pain, especially from myocardial infarction - Acute pulmonary oedema. Dose Up to 5mg by slow iv injection (may be repeated). Contraindications - Acute respiratory depression - Care in head injury. Side-effects Respiratory depression, nausea and vomiting, drowsiness, hypotension, tachycar dia, pinpoint pupils Notes - Naloxone (Narcan ) must always be available if opiate analgesics are being used Duration of action 1 \200\2232 hours - Nausea and vomiting is less troublesome than with mo rphine. CHAPTER 5 Analgesia and anesthesia 368 Fentanyl Description Extremely lipid-soluble, prompt-acting, potent synthetic opioid which is more potent than morphine. 100 g fentanyl and 10mg of morphine are equipotent. Presentation - 50 g/ml \200\2242ml and 10ml ampoules for intravenous injection - Also avai lable as cutaneous patches for intractable cancer pain. Effects Rapid onset analgesia (within as little as 2 minutes). Indications Severe acute pain. Dose - By iv injection 50 \200\223200 g, then 50 g as required - Child: 3 \200\2235 g/kg , then 1 g/kg as required. Contraindications See morphine. Side-effects - See morphine - May produce bradycardia of vagal origin, but maintaining bloo d pressure and cardiac output. Notes - Duration of action 30 \200\22360 minutes - May be given nasally in the same dose. USEFUL ANALGESICS: OPIOIDS1 369 Morphine Description An opiate analgesic. Presentation - Morphine sulfate 10mg/ml, 15mg/ml, 20mg/ml, and 30mg/ml \200\2241ml and 2ml ampoules Morphine sulfate 10mg/ml \200\2241ml pre-filled syringe - Morphine sulfate 1mg/ml \200\2241 0ml pre-filled syringe - Larger-volume vials are available but are intended for intravenous infusion preparation. Effects Binds to opiate receptors resulting in analgesia, euphoria, and respiratory depress ion. Indications Acute severe pain. Dose Morphine should be given by intravenous injection in small aliquots titrated to effect . An initial dose of 5mg is appropriate for an adult male, 2mg for smaller or older patient s. Doses of up to 30mg may be required in fit young men with severe pain. Children: up to 1 month, 37.5 \200\22375mg/kg; 1 \200\22312 months, 50 \200\223100mg/kg; 1 \200\2235 years, 1 \200\2232mg; 6 \200\22312 years, 2 \200\2235mg, all by intravenous injection Contraindications Acute respiratory depression. Side-effects Nausea and vomiting, drowsiness, respiratory depression, hypotension, hallucin ations. Acute allergic reactions. Notes The labeling on ampoules of proprietary morphine is identical except for the concentr ation. It is imperative that this is carefully checked if dosing errors are to be avoided. Morphine should always be administered in a concentration of 1mg in 1ml (10mg in 10ml). An antiemetic should be administered with any intravenous opiate. However, the use of Cycli morph (morphine/cyclizine) is not recommended. Naloxone and equipment for mechanical vent ilatory support MUST be available when morphine (or any other opiate) is administered. Morphine has a duration of action of about 2 hours. CHAPTER 5 Analgesia and anesthesia 370 Pethidine Description Synthetic opioid with a shorter duration of action than morphine. Presentation - 50mg/ml in 1ml and 2ml ampoules for injection - 10mg/ml in 5ml and 10ml ampo ules - Oral pethidine is not suitable for pre-hospital use. Effects - Analgesia - Obstetric analgesia (pethidine does not delay labor) - Atropine like effects \200\224blurred vision, dry mouth. Indications - Moderate pain - Obstetric pain. Dose - 20 \200\22350mg by slow iv injection - 50 \200\223100mg sc or im for obstetric analgesia. Contraindications - Patients taking monoamine oxidase inhibitors - Acute respiratory depres sion - Care in head injury Side-effects - See morphine - There is no evidence to suggest that pethidine has less effec t than morphine on the sphincter of Oddi Notes - Onset within 10 minutes; duration of action 1 \200\2232 hours - Pethidine is associ ated with a greater risk of hypotension because of its alpha blockade, it is NOT RECOMMENDED for pre-hospital use. This page intentionally left blank CHAPTER 5 Analgesia and anesthesia 372 Tramadol Description A synthetic opiate with additional actions (see below). It is a non-se lective OP1 and OP3 receptor agonist, acting mainly at the OP1 receptor. Presentation Tramadol hydrochloride 50mg/ml \200\2242ml ampoule. Effects Tramadol has opioid and non-opioid mechanisms of pain relief. It inhibits reuptake of 5HT and noradrenaline. It inhibits noradrenaline uptake and enhances serotonin release. Indications Moderate to severe pain. Dose 50 \200\223100mg iv every 4 \200\2236 hours. Contraindications See morphine, also epilepsy. Side-effects - Tramadol is claimed to be less likely to cause constipation and respiratory depression than other opioids Confusion, fits, and anaphylaxis - Nausea Pre-hospital use of tramadol is not recommended. USEFUL ANALGESICS: OPIOIDS1 373 Naloxone Description A competitive opiate antagonist. Time to onset 2 \200\2233 minutes. Du ration of action 20 minutes. Presentation - 400 g/ml \200\2241ml ampoule - 400 g/ml \200\2241ml, 2ml, and 5ml pre-fill ed syringe - 1mg/ml \200\2242ml pre-filled syringe Effects Reversal of opioid effects. Indications - Reversal of therapeutic overdose of opiates - Treatment of opiate poisoning ( recreational overdose) - Treatment of unexplained loss/reduction of consciousness. Dose - 0.4mg (400 g) \200\2232mg repeated at intervals, as required, to a maximum of 10mg If naloxone is given to exclude opiates as a cause of loss of conscious- ness, a dose of 10mg should be given Children: iv 10 g/kg, subsequent dose of 100 g/kg if no response. Contraindications Caution in patients who are physically dependant on opiates; will precipi tate pain in patients given opiate for analgesia. Side-effects Nausea and vomiting, tachycardia. Notes Naloxone is short acting. As a result, when long-acting opiates are being reversed, r epeated doses may be needed. Drug abusers may leave the scene after a first dose only to co llapse as the naloxone wears off. In order to reduce the likelihood off this, either the op iate can be reversed only enough to ensure adequacy of respiration before arrival in hospit al, or a similar dose to the intravenous one given above may be given INTRAMUSCULARLY in ad dition. Sudden reversal of opioid overdosage in opioid-dependant patients can produce cardiac arrhythmias, hypotension, and convulsions. CHAPTER 5 Analgesia and anesthesia 374 Treatment of opiate overdosage Opioid overdosage may be absolute (excessive administration) or relative (normal dosage given to compromised patients, commonly hypovolaemic producing excessive plasma levels). The clinical features are: - Sedation - Respiratory depression - Miosis Untreated, overdosage may lead to: - Respiratory arrest - Cardiac arrest Treatments include standard ABC management: - Securing the airway - Supplementary oxygen - Supporting ventilation - Intravenous access - Reversal with Naloxone. USEFUL ANALGESICS: OPIOIDS1 375 Antiemetics Nausea and vomiting are common following opioid administration. Most practition ers give an antiemetic proceeding opioid administration. Symptoms are due to stimulation of the chemoreceptor trigger zone in the fourth ventricle or direct stimulation of the vomiti ng center in the medulla oblongata or the vestibule. For more details, see Chapter 4 (Formulary): Cyclizine, p.319 - Metoclopramide, p.335 - Ondansetron, p.341. CHAPTER 5 Analgesia and anesthesia 376 Other analgesics Mild to moderate pain may be managed by paracetamol and non- steroidal ant i-inflammatory drugs (NSAID). Pre-hospital usage may be limited by the route of administrat ion and the adequacy of pain relief. Aspirin, see p.312 Paracetamol, see p.345 Ibuprofen, s ee p.330 Voltarol, see p.323 Compound analgesics, see p.318 OTHER ANALGESICS1 377 Nitrous oxide/oxygen 50:50 (Entonox) Description Entonox is a 50:50 mixture of oxygen and n itrous oxide (N2O). Nitrous oxide is a colorless, sweet-smelling, non-irritant, non-inflamm able gas. It is insoluble in blood, hence its rapid clinical effect, and 15 times more solu ble than nitrogen in plasma. Presentation Various sizes of blue cylinder with a white and blue mantle. Self administered with override valve. Effects Analgesia without loss of consciousness. Indications - Analgesia for moderate pain in fully conscious individuals - Analgesia for sh ort painful procedures - Rapid onset within 60 seconds, analgesic effect for 3 \200\2234 mi nutes. Dose Titrate to effect. Usually self administered using a demand valve. May be overridden b y medical staff. Overdosage does not occur with self admin istration. Contraindications Contraindicated in patients in whom an air-filled cavity exists into whic h nitrous oxide can diffuse. These conditions include pneumothorax (so contraindicated in s ignificant chest injury), the \200\230bends \200\231 (so contraindicated in patients follo wing diving), and open head injuries. Side-effects See above. Notes At temperatures less than \200\2237*C, nitrous oxide/oxygen mixtures will separate. This may lead to inhalation of pure oxygen, with no analgesic effect, followed by pure nitr ous oxide leading to hypoxia. A few shakes of the cylinder will have no effect, on this sep aration. Entonox MUST be kept above \200\2237*C, even if this means transferring it to you r vehicle immediately before departure. CHAPTER 5 Analgesia and anesthesia 378 Ketamine Description A dissociative anesthetic/analgesic in the form of a white crystalloid powder Presentation - 10mg/ml \200\22420ml vial for injection - 100mg/ml \200\22410ml vial for injection. Effects Ketamine has the following features: - It is powerfully analgesic i n subanaesthetic doses - Protective glottal reflexes are relatively preserved - It does not normally cause respiratory depression at conventional doses - It has a long shelf life - I t does not cause hypotension, but ketamine-induced hypertension makes it relatively contraindicated in head injury - It is relatively safe in patients with a full stomach. Indications - Pre-hospital anesthesia for extrication or short procedures Analgesia. Dose Anesthesia: im 5 \200\22310mg/kg (provides 12 \200\22325 min of surgical anesthesia, effective after 4 \200\22315 min) Iv 1 \200\2232mg/kg (provides 5 \200\22310 min of surgical anesthesia, effective after