First Impressions are Scary!
My first rotation in intensive care! Behind me are the days of the agitated patient at 4am; restless and pulling out cannulas and catheters. No more bleeps to deal with the elderly gent who by day is the sweetest, kindest person you could ever have the pleasure of meeting; but by sun-down becomes a man possessed, educating the hospital on new-found profanities.
On ITU, everyone is calm and relaxed, if not sedated and unconscious?? I know ITU will bring lots of new challenges, but at least the above situations are well and truly behind me…. I was quite wrong!
I discovered very quickly that agitation and delirium are a huge issue here; in fact, most patients suffer with it at some point or other. All of the issues contributing to delirium amongst general ward patients are still ever present, but they are now augmented by the fact that every limb / orifice seems to be needled, lined, or intubated!
Patients are attached like dormant puppets to racks of pumps and hi-tech machines bleep and alarm, irradiating the ceiling with a cacophony of lights 24hrs a day / 7 days a week. They are breathing artificially through tubes you would laugh at were you passed one to go snorkeling with. They are placed behind facemasks and hoods that look like fish-bowls, causing claustrophobia, inability to eat or drink and inability to communicate properly! Then, there’s even worse – the new piece of plastic sticking out the front of their neck stopping them from speaking, even though there’s nothing in their mouths. To us, these interventions become standard practice, but is it really any wonder these patients become agitated and delirious with all of this going on?!
As a (very) junior doctor on ITU, this is a challenge. What do I do when I’m called to a patient at 4am now? I haven’t seen anyone reminding me of the wrestling patient we discussed earlier, but now things are infinitely more worrying. Now, the agitated lady in bed 3 is fighting the ventilator and pulling her mask away, so her gas is becoming very concerning, very quickly. She is pulling at all her lines and has managed to pull her art-line out, and putting that back in to monitor her response to the vasopressors is going to be interesting! To add fuel to the fire, her heart rate is now soaring up and through the roof. She has still managed to whack one of the nurses with a surprisingly powerful left hook.
Sedation in critical care, I am coming to realize, is about more than just ensuring patients have a good night’s sleep and are well rested. Now it has become a major factor in whether they will ever get out of the unit at all. We can’t simply brush this under the carpet, as 80% of patients will suffer from this awful condition during their ITU stay. The therapies on this unit, can literally mean life or death. As a junior on ITU, having a system or framework to deal with this is vital. there is a temptation to titrate medications to achieve adequate sedation, but I think a good starting point is to ask a simple question first…
Why is this patient agitated?
We strongly encourage you to read the Finfer et al paper on this topic. It re-emphasizes that pain is reported as the most common memory patients have of their time in ITU; this is no surprise! Many are post-operative patients, others have had interventions that have been necessary and lifesaving, like CPR, but are incredibly painful afterwards. We tend to forget about all of this, focusing on the here and now, the monitors and the goals of the day. Remember, they have to cope with the added distractions of the foreign pieces of metal and plastic we have placed into / onto them, in order to get our monitors to glow up with the numbers we want. These were probably extremely painful at the time, and indeed may become more so over the course of their stay.
How about those tubes…are they blocked? Always ask yourself this. Just remember situations when you are desperate to go, but there is just no way you can! Your body goes into sympathetic overdrive…that stretched bladder making you feel sick, distressed, tachycardia and sweaty. A distended bladder is a silent physiological challenger you don’t want to miss.
Many of these factors are merely the start of this treacherous journey; what is important is that we care, recognize and treat these issues as soon as we can pick them up. The silent, still patient often hides pain…so it’s no wonder some of them hit the roof when they can actually make some semblance of an attempt to communicate. Many sedative regimes are reflexive and do not consider analgesia first; I have learned that this should be the number one driver for agent selection. See here.
They spend most of their day lying down in that famous, ‘semi-recumbent position, staring at the same spot on the ceiling. Can you imagine how awful this can be, particularly to people so active in their normal day-to-day lives? This is not only distressing and claustrophobic, but amplifies the potential for those dreaded pressure ulcers.
ITU is loud, bright and busy to say the least! Alarms become white noise to us, but are like drills to the temples of the patients. Imagine how daunting it is to wake up into this environment. Simple reassurance and orientation statements can help alleviate anxiety and calm our patients. One of the consultants I work with regularly tells disorientated or agitated patients where they are, what time of day it is and what’s happening around them. This seems to go miles for the patients. It is all too easy to forget to talk to the patients in the same way you would with someone fully interactive down on the wards…there really should be no difference. I have realized that the jokes regarding anaesthetists and ITU physicians being slightly sub-par on the communication front is entirely unfounded, in fact I have witnessed some of the best communicators in action under extremely difficult circumstances.
Potential new problems
It is very important to remember that this anxiety may be a result of an adverse change in the patient’s clinical circumstances. They may have acquired an infection, they may be brewing SIRS / Sepsis, their renal function may be on the way out and the corresponding dis-electrolytaemias they are developing may be bathing their brain, fighting against normal neurotransmitter equilibrium. But…we are armed with various luxuries in ITU, particularly the fact we can sample blood easily and often very rapidly to ascertain the cause. Similar cohorts of patients on the wards are not so blessed! Agitation and delirium are different and awareness of this is vital.
As a junior on ITU, the number of new drugs I have come across in a mere 2 months has been quite phenomenal. I am forever consulting an app, perusing the BNF, scouring the Trust intranet or asking for advice regarding some new medication I have never heard of. Just looking at the electronic chart of your average patient makes your hair stand on end! It is unsurprising that the number of potential interactions are legion. I am often surprised the patients’ blood types aren’t converted to propofol or midazolam, or any of the other concoctions we are flooding into them! These meds can be the culprits of confusion, and their withdrawal the converse; the cause!
Another thing to note is that we are very focused upon commencing the ITU, ‘life saving meds’, but we often take for granted what they were on before they got into this mess.
Don’t forget the fags and the booze! Alcohol withdrawal is a big player on the delirium/confusion team. I am sure you have seen the effects of alcohol withdrawal amongst patients on the ward. A reducing regime of chlordiazepoxide could help your patient out, and don’t forget nicotine! Your 20 a day smoker, whether they are in as a result of the damage smoking has done or not, may be craving that sympathetic buzz they are used to every day. There are no ET tubes we can ethically attach a cigarette to, so perhaps pop on a patch! The pharmacists are so helpful with many of these withdrawal aspects.
So… we have ascertained that delirium is a complex beast!
Whats the RASS?
What’s the CAM-ICU Score?
What’s the best medication to give?
Having done some reading around this topic, this is very much THE question! There is a wealth of discussion and research around finding the perfect combination in order to achieve adequate sedation.
All else has failed and you are now onto the pharmacological options. A nice little pathway to consider is shown below, and this is mainly to get you to think about what you are doing and WHY.
As a starting point (and as above in the diagram), the literature asks us what our goal is for sedation? Does this patient require deep continuous sedation due to severe respiratory failure, intracranial hypertension or refractory seizures; or lighter sedation? Due to advancement in ventilator technology, we don’t have to ‘flatten’ patients like we used to in order to make them ventilator or tube tolerant. Still though, each individual situation requires individual assessment to determine the correct sedation – long vs short term, anxiolysis vs analgesia, deep vs light.
Take a look at this lovely article below:
We always ask ‘ should we do a sedation hold today’? Massively important! Those who didn’t receive a daily sedation hold and received continuous sedation essentially faired worse and stayed on the vents for longer. See here. It also holds that delirium and agitation may also be minimised with this approach.
There are several important aspects to the ideal sedative agent(s): analgesia, hypnosis and anxiolysis being the ideal pharmacodynamic properties. They ideally should also possess good pharmacokinetic properties too – predictable elimination, distribution and titratability. However, there is currently no one drug that satisfies all the ideal criteria and there is little evidence suggesting a superior agent over another, which is why we use a combination of drugs. Furthermore, no particular combination of drugs has been shown to reduced mortality in critical care.
Bearing all this in mind, let’s move on to talk about the different medications available to us on ITU. The table below shows an excellent comparison of the commonly used agents in intensive care, highlighting both their pharmacokinetics but also their adverse effects.
So, to nutshell this, we want to:
- Optimise patient comfort
- Facilitate patient-ventilator synchrony
- Optimize oxygenation
A little helper for you!
- Common place in intensive care
- Used when aiming for good sedation in conjunction with anxiolysis. All have relative anticonvulsant effects.
- Modulation of the inhibitory neurotransmitter GABA by binding to GABAa gated channels centrally
- Increase the frequency of chloride channel opening events which leads to inhibition of excitatory action potential
- Only anterograde amnesia
- Have an opioid-sparing effect by moderating the anticipatory pain response
- Cardiovascular comprise, volume depleted or distributive states will affect the metabolism of benzodiazepines which are extensively metabolised by the liver.
- Higher risk of accumulation given the long half-life of diazepam; even shorter acting midazolam will accumulate over longer infusions.
- Other adverse effects include withdrawal and dependence states after longer exposure.
Initial dose: 2-2.5mg
Titration doses: 1mg
Total dose : 3.5-7.5mg
0.15-0.2mg/kg (0.3-0.35 without premedication)
Sedation on ITU
Loading dose: 0.03-0.3mg/kg in increments of 1-2.5mg
Maintenance dose: 0.03-0.2mg/kg/h
- High lipid solubility
- Onset: 2-3 minutes
- Duration: variable (Accumulates in fats)
- Avoid if hepatic/renal failure
- Inhibition of midazolam metabolism has been reported with inhibitors of cytochrome P450
- Obese (high lipid soluble) or patients with reduced serum albumin levels have prolonged sedative effect
0.05mg/kg (3.5mg for an average 70kg man) IV
Sedation will be evident after 5-10 minutes and maximal loss of recall will occur after 30-45 minutes.
Acute Anxious State
0.025-0.03mg/kg (1.75-2.1mg for an average 70kg man) IV Repeat 6 hourly.
Useful bolus medication due to longer half-life and lower clearance.
- Less lipid solubility
- Onset: 5-10min
- T1⁄2 : 12- to 15hrs
- Once metabolised, has a relatively high clearance and is therefore more useful as an infusion.
**Benzodiazepine antagonist: flumazenil – is not recommended after prolonged benzodiazepine therapy – risks of inducing withdrawal symptoms and increasing myocardial oxygen consumption. If you have to give, use lower dose of 0.15 mg.
2) IV anaesthetic agents
1.5–2.5 mg/kg of Diprivan 1% (May need to adjust up in paeds)
4–12 mg/kg/h usually maintain satisfactory anaesthesia
Repeat Bolus Injections
Increments of 25 mg (2.5 ml) to 50 mg (5.0 ml) may be given according to clinical need
0.3–4 mg/kg/h of Diprivan 1%
Sedation for acute procedures
0.5–1 mg/kg over 1– 5 minutes for onset of sedation
Titrate to 1.5–4.5 mg/kg/h.
- Short acting and therefore appropriate to be used as an infusion
- Potentiation and direct activation of GABA-A receptors.
- Increase extracellular dopamine and may block dopamine reuptake
- Onset: 1-2min
- T 1⁄2: 1-3 hrs
- Elimination by hepatic conjugation to inactive metabolites
- Easily titratable to patient response.
- Doesn’t accumulate due to its high clearance rate and even after a longer infusion, consciousness recovers quickly.
- Both renal and hepatic dysfunction, a common occurrence in critical care patients, does NOT affect propofol’s metabolism
- Widely known to cause hypotension by reducing systemic vascular resistance. Can also lead to bradycardia, myocardial depression, green discolouration of the urine. These factors obviously present an issue when presented with a patient with cardiovascular compromise requiring sedation.
- Worth a mention here is propofol infusion syndrome which limits the long-term use of propofol, especially at higher infusion rates and in younger children
- Increased serum triglycerides – potential (1.1 kcal/mL from fat )
- Pain upon peripheral venous injection
- Pancreatitis (increased ‘serum lipase’) + Zinc depletion
- Vehicle may cause allergic reaction – Prepared in “egg” & “soyabean oil”Requires a dedicated i.v. catheter when administered as a continuous infusion because of the potential for drug incompatibility and infection. Hence may contain preservatives
- May have “Sodium metabisulfite” (propofol, Gensia Sicor) which may produce allergic reactions in susceptible patients.
- May have “Edetic acid” (Diprivan, AstraZeneca) and the manufacturer recommends a drug holiday after more than seven days of infusion to minimize the risk of trace element abnormalities.
100mg to 150mg intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution.
A repeat dose of 100mg to 150mg may be given after one minute.
Average dose for an adult of 70kg is roughly 200mg to 300mg (8mls to 12mls of a 2.5% w/v solution) with a maximum of 500mg.
75mg to 125mg (3mls to 5mls of a 2.5% w/v solution)
Raised ICP states
Intermittent bolus injections of 1.5 to 3mg/kg
- Tendency to accumulate due to lower clearance rates and at higher doses saturates hepatic enzyme leading to zero order metabolism. Occasionally used in Neuro-ITU.
- Thiopental sodium causes respiratory depression and a reduction in cardiac output and may precipitate acute circulatory failure in patients with cardiovascular disease, particularly constrictive pericarditis.
- Ketamine induces sedation, immobility, amnesia and marked analgesia. The anaesthetic state produced by ketamine has been termed “dissociative anaesthesia” in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centres and pathways (reticular-activating and limbic systems).
- Numerous theories have been proposed to explain the effects of ketamine, including binding to N-methyl-D-aspartate (NMDA) receptors in the CNS, interactions with opiate receptors at central and spinal sites and interaction with norepinephrine, serotonin and muscarinic cholinergic receptors. The activity on NMDA receptors may be responsible for the analgesic as well as psychiatric (psychosis) effects of ketamine.
- Ketamine has sympathomimetic activity resulting in tachycardia, hypertension, increased myocardial and cerebral oxygen consumption, increased cerebral blood flow and increased intracranial and intraocular pressure. Ketamine is also a potent bronchodilator.
- Clinical effects observed following ketamine administration include increased blood pressure, increased muscle tone (may resemble catatonia), opening of eyes (usually accompanied by nystagmus) and increased myocardial oxygen consumption.
IV – 1 mg/kg to 4.5mg/kg
The average amount required to produce 5 to 10 minutes of surgical anaesthesia has been 2.0 mg/kg.
IM – 6.5 mg/kg to 13 mg/kg
A low initial intramuscular dose of 4 mg/kg has been used in diagnostic manoeuvres and procedures not involving intensely painful stimuli.
A dose of 10 mg/kg will usually produce 12 to 25 minutes of surgical anaesthesia.
A solution containing 1 mg/ml of ketamine in dextrose 5% or sodium chloride 0.9% is suitable for administration by infusion.
General Anaesthesia Induction
0.5 – 2 mg/kg as total induction dose.
Maintenance of anaesthesia
10 – 45 microgram/kg/min (approximately 1 – 3 mg/min).
- Notoriously popular in the pre-hospital setting, in the ED and occasionally on the ITU for specific circumstances where airway and CVS compromised are absolute ‘no no’s’.
- Onset: 1 min
- T1⁄2: 10-15min
- Positive inotropic action / Induces vasoconstriction / Inhibits endothelial nitric oxide production
- Increases myocardial oxygen demand
- Bronchodilator activity / Increase oral secretions
- Provides analgesia + amnestic + sedative effects
- Preserves respiratory drive – “awake” intubation
- Most hemodynamically stable of all of the available sedative induction agents
- Beneficial effects on stunned myocardium
- Minimize the adverse sympathetic stimulation of laryngoscopy
- Increased oral secretions
- Potential for exacerbating myocardial ischemia.
? Risk for elevating ICP – “does not increase cerebral blood flow or ICP if normal carbon dioxide levels are maintained”
Opiate receptors are coupled with G-protein receptors and binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. This decreases intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon.
Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.
- Awareness is needed regarding altered pharmakokinetics in the critically ill due to:
- Hepatic dysfunction
- Decreased hepatic blood flow
- Renal dysfunction
- Alteration in volume status and plasma protein binding capacity
- Opiates are commonly used in intensive care due to their sedative, analgesic and anxiolytic effects, aiding tolerance of more invasive interventions such as ET-tubes and permitting ventilator synchrony.
- Should all be titrated to a validated pain score, where applicable.
- Recent comparative trials now emerging regarding opioids and ventilator associated days / weaning dynamics.
- Adverse effects of opioids are commonly known to include constipation via reduced gut motility which reduces enteral nutrient absorption, hallucinations, delirium and respiratory depression.
IV 0.1mg/kg titrate to effect
- Common choice of opiate, metabolised in the liver to form potent active metabolites with strong analgesic properties, but these readily accumulate in renal failure.
- Predominantly μ-opioid receptor activity
- T1⁄2: 1.7-4.5hrs
- 60% of morphine is converted to morphine-3-glucuronide (inactive), and 6–10% is converted to morphine-6-glucuronide (1/2 as active).
- Hypotension may result from vasodilatation
- Active metabolite may cause prolonged sedation in the presence of renal insufficiency.
Ventilated patients may be given a loading dose as a fast infusion of approximately 1 microgram/kg/minute for the first 10 minutes, followed by an infusion of approximately 0.1 microgram/kg/minute.
Lower infusion rates, e.g. 0.05 – 0.08 microgram/kg/minute, are required if spontaneous ventilation is to be maintained.
- Another commonly used sedative / analgesic drug, but tends to accumulate due to redistribution – useful for its medium duration of action.
- μ-opioid receptor activity
- Highly lipophilic
- Rapid onset 2-5mins
- Lasts 30 mins or so
- T1⁄2: 2-4hr
- Repeated dosing may cause accumulation esp. in renal dysfunction
- Less nausea, as well as less histamine- mediated itching, in relation to morphine
Sedation on ITU
0.5-1mcg/kg/min or 250-1000mcg/hr infusion rates
- Accumulates less, due to a higher clearance and is thus shorter acting. This is often the preferred titratable opioid in ITU.
- Pharmacology stuff:
- Analogue of fentanyl with around 1/4 the potency
- Around 1/3 of the duration of action
- Onset of effects 90 seconds
- Duration 5-10mins
- Less cardiovascular complications but stronger respiratory depression
- Hypotension esp. in hemodynamically unstable / sympatholysis and vagally mediated bradycardia occasional
- Histamine release
- Depression of level of consciousness
- Gastric retention and ileus
- May increase intracranial pressure with traumatic brain injury, although the data are inconsistent.
Cover for acute procedure
0.025-0.1mcg/kg/min spontaneous breathing
- Being used more and more frequently and is receiving a lot of positive press on ITU. There have been many discussions regarding its usage on ITU and we have certainly posted various items on this before:
- Remifentanil doesn’t rely on renal or hepatic metabolism, which is a useful plus in the critically unwell patient.
- Pharmacology stuff:
- Specific μ-receptor agonist
- Potent (250 times morphine)
- Onset: 1 minute
- T1⁄2 = 4 minutes after a 4-hour infusion.
- Has ester linkage – rapid hydrolysis by non- specific tissue and plasma esterases to metabolized to remifentanil acid which is almost inactiveàexcreted in kidneys
- Synergism between remifentanil and other hypnotic drugs (such as propofol). This means the dose of hypnotic can be substantially reduced resulting in greater hemodynamic stability
- When weaning remifentanil, be vigilant! The opioid effect will have worn off 10-15mins after cessation of the infusion. Advantageous when waking patients up from sedation and weaning, but be prepared to step in within this time period with longer acting analgesia!
- No dose adjustments needed in renal or liver disease
- Reduction in sympathetic nervous system tone can be profound, as can respiratory depression
- Bolus injections of remifentanil may cause ‘thoracic muscle rigidity’ with difficult mask or pressure-controlled ventilation
- Acute withdrawal syndrome recognized
4) Neuroleptic agents
- From the English prefix ‘neuro’, relating to the nervous system and the Greek ‘leptikos’, meaning disposed to take. Quite literally meaning the disposition of nerves that are being taken?!
- Essentially these agents provide sedation via a reduced state of consciousness, alongside some anxiolysis, reduced motor function and reduced interaction with one’s environment.
- They exert a stabilizing effect on cerebral function by antagonizing dopamine-mediated neurotransmission at the cerebral synapses and basal ganglia.
Rapid control of severe acute psychomotor agitation
5 mg intramuscularly
May be repeated hourly until sufficient symptom control is achieved.
In the majority of patients, doses of up to 15 mg/day are sufficient.
The maximum dose is 20 mg/day.
Acute treatment of delirium when non-pharmacological treatments have failed
1 to 10 mg intramuscularly.
The maximum dose is 10 mg/day.
Postoperative nausea and vomiting
1 to 2 mg intramuscularly, at induction or 30 minutes before the end of anaesthesia.
- It has advantages in possessing heavy sedative properties relating to neurolepsis, but with minimal respiratory depression.
- Patients can become very flat in overdose
- Long half-life (18–54 hours)
- Loading regimen starting with a 2-mg dose, followed by repeated doses (double the previous dose) every 15–20 minutes while agitation persists
- Rare, Dose dependent QT prolongation
- Slowly eliminated active metabolite of haloperidol appears to cause EPS
- May prolong the duration of posttraumatic amnesia
A single deep intramuscular injection of 25-50mg followed by oral therapy will suffice in many cases, but the intramuscular dose may be repeated if required at 6 to 8 hour intervals.
- Utilised very occasionally, mainly due to its vast mechanism of action on acetylcholine, serotonin, noradrenaline and histamine receptors. But it had so many side effects, it has become obsolete on ITU.
For the treatment of schizophrenia
Quetiapine should be administered twice a day. The total daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4)
For the treatment of moderate to severe manic episodes in bipolar disorder
Quetiapine should be administered twice a day. The total daily dose for the first four days of therapy is 100 mg (Day 1), 200 mg (Day 2), 300 mg (Day 3) and 400 mg (Day 4). Further dosage adjustments
The usual effective dose is in the range of 400 to 800 mg/day.
- Second generation atypical antipsychotic
- Serotonin and Dopamine antagonist
- Most sedating of all anti-psychotics
- Neuroleptic malignant syndrome / Tardive dyskinesia
5) Alpha agonists
- Interesting agents that provide analgesia, sedation and anxiolysis via alpha 2 adrenoceptor agonism.
- Clonidine is used frequently on ITU as it provides the aforementioned effects, again with minimal respiratory depression.
- Its use is especially effective in the agitated or withdrawing patient, but takes time to reach a steady state, requiring continuation of current sedation. The best approach should be to commence it in parallel with the primary sedative agent, before a gradual wean down to leave it remaining on.
Initial infusion rate of 0.7 micrograms/kg/h
Dose range 0.2 to 1.4 micrograms/kg/h in order to achieve the desired level of sedation, depending on the patient’s response.
- SEDCOM – There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia.Centrally acting α2 agonist – (like clonidine but 7 times stronger)
- MENDS – In this subgroup analysis, septic patients receiving dexmedetomidine had more days free of brain dysfunction and mechanical ventilation and were less likely to die than those that received a lorazepam-based sedation regimen. These results were more pronounced in septic patients than in non-septic patients. Prospective clinical studies and further preclinical mechanistic studies are needed to confirm these results.
- BJA Paper -From the clinician’s and patient’s perspectives, dexmedetomidine is a safe and acceptable sedative agent for those requiring intensive care. The rate pressure product is reduced in patients receiving dexmedetomidine, which may protect against myocardial ischaemia. Dexmedetomidine reduces the requirement for opioid analgesia.
- T1⁄2: 6min- 2hrs
- Approved by FDA 1999
- Highly protein bound
- Arousability is maintained at deep levels of sedation, with good correlation between the level of sedation (Richmond agitation-sedation scale) and the bispectral (BIS) EEG
- Sedation induced by dexmedetomidine has the respiratory pattern and EEG changes commensurate with natural sleep – “activates endogenous non–rapid eye movement sleep– promoting pathways”
- Reduction of central CNS activity (alpha 2a) – hypotension
- Reduction of presynaptic NE release (alpha 2a & 2c) – hypotension
- Stimulation of Vascular Smooth Muscle cells (alpha 2b) – increase BP
- Stimulation of endothelium
- Stimulation of central imidazoline receptors
- Vagomimetic activity – bradycardia
- Suppress shivering (alpha-2B in the hypothalamic thermoregulatory center)
- Attenuation of ischemia-reperfusion injury
- Reduction in the incidence of delirium / time on mechanical ventilation / tachycardia and hypertension
- Opiate sparing
- Hypotension appears to be similar between benzodiazepines and dexmedetomidine 20-30%.
- Little effect on respiratory drive/alertness but “may cause upper airway obstruction”
- Unlike clonidine, cessation of administration does not appear to be associated with rebound hypertension or agitation
- Bradycardia – (doses of ≤0.7 μg/kg/h, bradycardia occurred in less than 15% of patients)
- Average response is 20% reduction in HR
- Usually is not clinically significant unless patient has co-existing cardiac disease
- Baroreflexes are reset but intact – hence HTN will reduce HR further
The table below gives a quick glance summary of the advantages and disadvantages of the various medications we have discussed.
An nice example ITU sedation regime:
There are many medications involved in sedation, many are more as adjunctive as opposed to ‘sedative.’ Specifically, other forms of analgesia, (NSAIDs, paracetamol, nefopam, regional anaesthesia, gabapentin, amitriptyline. All may be involved in the overall sedation of an agitated patient but are primarily aimed and treating pain. Another notable adjunct are neuromuscular blockers. Thus seems like a bizarre statement, because they clearly do not cause sedation! But they are undeniably useful for certain situations relating to ventilation control and tolerance.
So where are we with this?
The FICM set out specific recommendations on the use of sedation. The first point they make is that as clinicians, we need to assess each individual clinical scenario and decide on the indication for sedation, as well as formulate a plan of what we are trying to achieve.
- What specific aspects of sedation are we hoping to address
- analgesia, hypnosis, amnesia, anxiolysis?
- Assessment protocols for pain and sedation.
- Achievement of a stable clinical state for each individual patient.
As a junior on ITU, it is inevitable that I am going to be the first port of call in dealing with the majority of delirious / agitated patients on ITU. That’s a fact I can’t escape and hence the importance of knowledge of this topic. I now feel that having read around the topic for this blog, I have accrued a greater awareness of the options I have when trying to manage these patients.
So now I know why the chap in bed 4 is on a titrating dose of ‘prop with a smidge of Alf’, and the lady in bed 6 is just on clonidine with haloperidol prn.
ITU is full of complex decisions, and this is by no means an exhaustive summary of the sedative options, but everyone must start somewhere. At least now I feel more comfortable with the thought process behind the prescription of sedation than I did before.
Written by: Dr Ben Martin CT1 ITU/Anaesthesia
Senior editor: Dr Jonny Wilkinson
Fantastic Intro Video to sedation:
Another brilliant video talk here: