Transcript SEDATIVES,ANALGESICS AND PARALYTICS

By Dr.Amena Fatima
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The International Association for the Study of Pain
defines pain as an “unpleasant sensory and
emotional experience associated with actual or
potential tissue damage,or described in terms of
such damage”.
pain can have deleterious consequences
• provoking anxiety
• contributing to lack of sleep
• worsening delirium
• increasing the stress response --Increased circulating catecholamines can
cause arteriolar vasoconstriction, impair tissue perfusion, and reduce
tissue-oxygen partial pressure . ,Catabolic hypermetabolism resulting in
hyperglycemia, lipolysis, and breakdown of muscle ,leading to impair
wound healing and increase the risk ofwound infection.
• causing respiratory embarrassment due to atelectasis and sputum retention
• causing immobility with venous and gut stasis.
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Pain suppresses natural killer cell activity ,, a critical function in the
immune system
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a caring and supportive ICU team, whom the patient can trust
warm and comfortable surroundings
attention to pressure areas
bowel and bladder care
adequate hydration and amelioration of thirst (e.g.moistening the
mouth).
early tracheostomy where indicated to reduce the
discomfort of endotracheal intubation
supplemental treatments such as acupuncture,
acupressure, massage and transcutaneous electrical
nerve stimulation (TENS).
Music therapy,relaxation.
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Pain management relies largely on the use of opioid analgesics,
regional anaesthic and other adjuncts.
Opioids : morphine and its analogues (e.g. diamorphine,codeine)
• semisynthetic and synthetic agents:
– phenylpiperidine derivatives (e.g. pethidine, fentanyl,
sufentanil, remifentanil)
– methadone
– thebaine derivatives (e.g. buprenorphine,oxycodone).
Local and regional anesthetics (e.g., bupivacaine).
Adjuncts:Nonsteroidal anti-inflammatory medications (e.g.,
ketorolac,ibuprofen), IV acetaminophen, and anticonvulsants, can
be used to reduce opioid requirement.
Four opioid receptor subtypes; mu,kappa,delta and nociceptin/orphanin FQ. These are Gprotein-coupled receptors that inhibit adenyl cyclase to reduce cAMP. This results analgesia
mediated at supraspinal, spinal and peripheral nerve endings.
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Opioids are titrated to effect by intermittent i.v. injection, or by continuous infusion. 1
mg/mL of morphine,or 20 µg/mL of fentanyl titrated to effect.
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Can also be administered via the subarachnoid, epidural, transdermal, oral, sublingual and
intranasal routes.
Side effects:
1.
wide inter-individual response.
2.
severe hypotension following rapid administration, particularly in hypovolaemic patients.
3.
prolonged duration of action, due to accumulation of parent compound and metabolites (e.g.
morphine and its major metabolites morphine-3-glucuronide and morphine-6-glucuronide) in
the elderly and inpatients with renal and hepatic dysfunction. Use of
drugs with shorter half-lives (e.g. fentanyl or sufentanil) or those with organ-independent
metabolism
(e.g. remifentanil) can reduce this problem.
4.
constipation, often requiring concomitant administration of aperients to promote regular
evacuation and prokinetics to prevent gastrostasis and allow enteral feeding.
5.
the development of tolerance.
6.
withdrawal symptoms on cessation or reduction of
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 Treatment is by reinstitution of and then slow
withdrawal of the opioid. Alternatively, symptoms
may be controlled by substitution for a long-acting
opioid (e.g. methadone), BZAs or α2-agonists.
The specific opioid antagonist naloxone has little role
to play in the ICU, except for the treatment of severe
hypotension, unwanted sedation or respiratory depression following opioid
usage or overdose.
IV opioids be considered as the first-line drug class of choice to treat nonneuropathic pain in critically ill patients.
Neuropathic pain, poorly treated with opioids alone, can be treated with
enterally administered gabapentin and carbamazepine in ICU patients with
sufficient
gastrointestinal absorption and motility .
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This is a synthetic, selective mu receptor agonist.
half-time of 4 minutes.
it causes sedation, tube tolerance and a slowed
respiratory rate.
The loading dose is usually 1 µg/kg.Continuous
infusion rates of 0.05–0.5 µg/kg/min are usually
required and a starting rate of 0.1 µg/kg/min is
recommended. Dosage alterations are usually in
increments of 0.025–0.1 µg/kg/min.
Due to the shorthalf-life, adequacy of response can be
assessed within 20 minutes.
Weaning should also be done by incremental dose
reductions due to the risks of rebound hyperalgesia.
Adding ketamine during the weaning process may
modulate this risk.
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Tramadol is a synthetic, racemic preparation.
The (+) enantiomer is a mu receptor agonist and serotonin
reuptake inhibitor, whereas the (−) enantiomer is a nor
epinephrine reuptake inhibitor.In addition to mu receptor
action, it also enhances the descending inhibitory pathways
involved in pain modulation.
It is useful for moderate to severe pain in the post operative
patient in doses of 50–100 mg i.v., p.o. or i.m. 4-hourly to
amaximum of 600 mg/day.
Patients are at risk of developing serotonin syndrome
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Short-term administration of Entonox (50%
nitrous oxide in oxygen) is still useful for
analgesia during painful procedures (eg:burns
dressings)
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Carried out by adequately trained personnel.
time-consuming,require additional staff to properly position the
patient and assist the proceduralist.
Serious complications (e.g.subarachnoid injection of local
anaesthetic or epidural haematoma during placement of epidural
catheters) as well as the risk of local anaesthetic toxicity.
informed consent,recent normal coagulation profile or correction
of abnormal profile, Platelet counts above 75 000/µL antiplatelet
agents should be ceased.
adequate training of nursing staff to monitor
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pain often emanating from multiple sources.
The requirement for i.v. sedation/analgesia.
The need to treat pain over a prolonged period, mandating
either repetition of the regional block or the placement of an
indwelling catheter (e.g. epidural catheter).
Indwelling catheters have a defined duration of insertion
(usually 3–4 days) before needing to
be removed due to increasing infection risk.
Pts with coagulopathy and thrombocytopenia.
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Ropivacaine 0.2% is used for regional infusions
and can be combined with an
opioid, such as fentanyl 2 µg/mL or 4 µg/mL,
for epidural infusion.
Ropivacaine;a single bolus of upto 3 mg/kg - a
maximum of 300 mg,while continuous infusion
rates should not exceed 400 µg/kg/h
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midazolam and propofol remain the
dominant medications used for ICU sedation,
with decreasing
lorazepam use, and rare use of barbiturates,
diazepam, and ketamine in the ICU
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a treatment: seizures,raised intracranial pressure, serotonin
syndrome and alcohol withdrawal.
For tolerating intubation, mechanical ventilation and active
cooling.
To reduce oxygen consumption by reducing patient arousal,
activity and anxiety.
To maintain the safety of patient and carers when dealing with the
hyperactive delirious patient.
palliation.
Providing adequate rest.
Reducing the distress of unpleasant sensations, invasive
treatments and monitoring.
Blunting awareness of the environment.
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• goal-directed sedation
• patient-targeted sedation protocols
• daily interruption of sedation
• intermittent sedation
• ‘analgosedation’ or analgesia-based sedation
• patient-controlled sedation.
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sedatives are freely adjusted (usually by the
bedside nurse) to attain a prescribed level of
sedation
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a structured approach to the assessment
of patient pain and distress, coupled with an
algorithm that directs drug escalation and deescalation based on assessment
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this strategy employs a goal of sedative and
analgesic titration to a desired depth of sedation.
The risk of excessive sedation is minimised by a
daily interruption of both sedative and analgesic
infusions until the patient awakens or exhibits
distress that mandatesresumed drug
administration, usually with an initial bolus
followed by a reduced infusion rate.
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Involves use of longer-acting sedative agents,
typically lorazepam,given by intermittent bolus
titrated via a sedation scoring system.
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Here sedation is notrequired as a treatment of their
disease process.
In these patients, opioid analgesia is instituted first,
and once pain is adequately controlled, verbal
measures are usedto calm the patient to a targeted
sedation level
. Major tranquillisers (e.g. haloperidol) are given for
delirium and only then are sedative agents (propofol)
used for short-term infusion andpromptly ceased.
Pros: shorter duration of mechanical ventilation
• shorter length of ICU and hospital stay
• economic benefit
• less need for diagnostic studies (e.g. computed axial
tomography (CT) scans) to assess impairedconscious state
• less ventilator-associated pneumonia
• a possible mortality benefit.
Cons:
• high self-extubation rates
• promotion of myocardial ischaemia
• triggering of a withdrawal syndrome.
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Gamma amino butyric acid (GABA) is a major neurotransmitter
involved in the complex process of sedation.
It binds to the alpha subunit of the GABA-A receptor and, by
activation, causes a conformational change that opens the ligandgated channel, allowing chloride ion influx into the neuron. This
hyperpolarises the neuronal membrane and reduces neuronal
activity leading to sedation.
The GABA-A receptor agonists used in intensive
care are benzodiazepines, propofol and barbiturates.
They all share amnesic, hypnotic, anxiolytic and anticonvulsant
effects, but have no analgesic properties.
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most widely used sedatives in ICUs.
BZAs are good anticonvulsant drugs and also provide some muscle
relaxation.
commonest agents used are midazolam,
lorazepam and diazepam.
BZAs (e.g. midazolam) are shortacting, water-soluble agents, there is
potential for accumulation of both parent compound and active
metabolites in patients with hepatic and/or renal dysfunction.
Midazolam, in doses of 0.02–0.2 mg/kg/h.
Longer-acting agents, such as diazepam, may be given by intermittent i.v.
injection (e.g. diazepam
5–10 mg) as necessary.
BZAs are often combined with opioids in a compound ‘sedative’ infusion.
This allows lower doses of BZA to be used, while capitalising on the
opioid effects of respiratory and cough suppression, to facilitate
mechanical ventilation and tube tolerance.
Flumazenil (flumazepil), the specific BZA antagonist, may be used to
reverse the effect of BZAs to reduce unwanted acute side-effects, such as
severe hypotension or respiratory depression, or to allow acute
neurological assessment of the sedated patient.
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i.v. anaesthetic agent propofol (2,6-di-isopropylphenol.
It binds to the beta subunit on the receptor and causes a
conformational change to the chloride channel.
It has a rapid hepatic and extrahepatic
conjugation reactions to inactive metabolites,short ½ life.
Caution is required in hypovolaemic patients or those with
impaired myocardial function as severe hypotension may result.
The diluent in which propofol is delivered is lipidrich( indeed
cause of hyperlipidaemia).
‘Propofol infusion syndrome’ particularly in paediatric patients,severe heart failure (preceded by metabolic acidaemia, fatty
infiltration of the liver and striated muscle damage).
Hyperlipidaemia may be a warning sign
for development of the syndrome and serum triglyceride
monitoring should be considered in patients at
risk.
Management requires immediate cessation of propofol and
cardiovascular supports, which may necessitate ECMO.
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Thiopentone is reserved for specific
indications, such as management of intractable
intracranial hypertension,treatment of status
epilepticus.
It is not commonly used as a general sedative
agent due to a long half-time.
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Volatile agents are useful for short periods of anaesthesia during
invasive procedures in the ICU.
They have classically been used for longer periods of sedation in
acute severe asthma, due to their bronchodilator effect.
• lack of a withdrawal syndrome• predictable offset independent
of renal or hepaticdysfunction
• cardioprotective effects• no tachyphylaxis• lower incidence of
delirium• ability to measure and titrate end-tidal
volatileconcentration.
The use of volatile anaesthetic agents for sedation in the ICU has
been limited by:
• the cost of prolonged administration
• the more complex set-up required for the administration of these
agents (vaporiser, scavenging apparatus, etc.)
• specific side-effects such as; ‘halothane’ hepatitis;
accumulation of fluoride ions and consequent renal
dysfunction (sevoflurane (fluoromethyl hexafluoroisopropyl
ether) and isofurane.
• occupational health and safety concerns (e.g. spontaneous
miscarriage)
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Ketamine acts by blocking NMDA receptors,has the following
characteristics:
• mild sedation
• amnesia
• analgesia
• reduced motor activity.
The lack of respiratory and cardiovascular depression at lower doses
makes this a relatively safe drug for use in the ICU.
Limitations to its use include hallucinations, and delirium during the
recovery/withdrawal phase. These may be ameliorated by BZA
administration.
Ketamine may be used specifically for sedation in
severe asthmatics (for its bronchodilator effect), inpatients following head
injury (for its effect at theNMDA receptor) or in patients where analgesia
is difficult (e.g. extensive burns).
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Butyrophenones (e.g. haloperidol) and phenothiazines(e.g.
chlorpromazine) are very useful agents for thesedation of
delirious patients in the ICU.
They act via a range of receptors including dopaminergic (D1 and
D2), alpha-adrenergic, histamine, serotonin and cholinergic
receptors.
Main actions include:
• reduced motor activity• apathy and reduced initiative•
sedation and drowsiness
• reduced aggression• antiemetic.
Unwanted effects with these drugs are common and include:
• extrapyramidal effects (dystonia, akathisia and parkinsonism)
• endocrine effects (e.g. lactation)
• anticholinergic effects ( blurred vision,dry
mouth,urinaryretention,constipation)
• hypotension
• neuroleptic malignant syndrome.
The advantage is that they can be used to gain control in difficult
situations, without major risk of respiratory depression.
haloperidol, diluted to a 1 mg/mLsolution.
Atypical antipsychotic agents, such as olanzapine and quetiapine
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Dexmedetomidine is a highly selective α2-agonist with
a half-life of 2 hours. It provides safe analgesia and
sedation in the ICU.
dexmedetomidine results in less delirium and
shorter time to extubation.
an effective treatment of agitated delirium in critically
ill patients.
A loading dose of 1 µg/kg over 10 minutes , Infusion
rates of 0.2–1.0 µg/kg/h
Side-effects may be predicted from the mechanism of
action and include hypotension and bradycardia.
Clonidine, an established long-acting α2-agonist,. The
usual i.v. dose range is 50–150 µg, 4–6 hourly.