Author - Dr Manoj Luthra | Dr Ramesh Gourishankar
 

Patients are on intermittent positive pressure ventilation, when they are shifted to the ICU from the operating theatre. Initial management during the postoperative ventilation in the ICU is with combination of an analgesics and a sedative. Commonly used analgesic is either Morphine or fentanyl and sedation is provided with dexmedetomidine or propofol. Midazolam is sometimes used as an alternative for sedation. In case the patient is restless and unable to maintain oxygenation or is hemodynamically unstable, he will also require muscle relaxants and commonly atracurium or vecuronium are administered. The sedative can be titrated to effect but full doses of analgesics should be given and increased further depending on patient parameters. Muscle relaxants are stopped as early as possible and any residual neuromuscular blockade is reversed prior to extubation.

 After extubation infusion rates of opioids and dexmedetomidine are reduced by about 50% to mitigate their sedative side effects and intermittent IV Inj paracetamol is introduced for its pain relieving and opioid sparing effect and is repeated at 6 hourly intervals. Subsequently, depending on the degree of pain, patients may continue to receive IV opioids for an additional day or so longer. When the surgical site pain starts subsiding, usually on second post op day, intravenous paracetamol is replaced by oral tablet given 6 hourly and the opioid infusion is replaced by trans-dermal fentanyl or buprenorphine 

Opioids are effective, relatively inexpensive, and are available for administration as stat IV medication or infusion. Even though OPIOIDS are very effective they are associated with sedation, respiratory depression, opioid induced constipation  and nausea, vomiting and paralytic ileus, and so patients need to be closely monitored. 

After the patient has been extubated, IV and oral paracetamol, is routinely used while in select refractory cases NSAIDS, magnesium, gabapentinoids, or dexamethasone and low dose ketamine infusion are options used to provide pain relief and shorten post op recovery. 

The doses of opioids can be significantly reduced with the addition of not only other non-opioid analgesic drugs but nerve and regional blocks.  Safety concerns have reduced the use of traditional neuraxial anesthesia techniques (spinal anesthesia / intrathecal morphine/ thoracic epidural analgesia etc). Paravertebral block is as effective as epidural with lesser hemodynamic side effects  but also carries some risk. Currently, ultrasound-guided fascial plane blocks have been shown to be effective and safe and are being used more frequently. 

Drugs and protocols used in post-operative pain management, however, vary with various units and doctor preferences.

OPIOID ANALGESICS

Morphine

Morphine is a potent analgesic and sedative alkaloid extracted from opium poppy and is the standard against which all other semisynthetic and synthetic opioids are compared. It acts mainly through mu opioid receptors which are distributed widely in the CNS and peripheral nervous system.  However, while providing dose dependent intense analgesia, morphine also has hemodynamic side effects, it reduces heart rate, blood pressure, and venous return which is due to its centrally mediated action on the sympathetic system and enhancement of vagal and parasympathetic tone. 

Morphine can be administered through various routes – intravenous as bolus or infusion, intramuscular, subcutaneous, neuraxial (spinal, epidural), local infiltration (arthroplasty), as well as oral for palliative care. 

The dose of morphine for Intravenous intermittent bolus dosing in adults in the ICU setting is a loading dose of 2- 10 mg, as indicated, followed by  2 - 4 mg every 1 to 2 hours or 4 to 8 mg every 3 to 4 hours1 (Fuschs B,Bellamy C)

As an IV infusion, the initial dose, for patients weighing less than 50 kg is 0.01 mg/kg/hr, with a dosage range of 0.01 to 0.04 mg/kg/hr. The dose for patients weighing 50 kg or more is 1 to 2 mg/hr 2 

Morphine is prepared in a dilution of 1mg /ml; 2 ampoules (15 mg/ampule) are diluted with NS to make 30 ml. Commonly used infusion rates are 1.5mg / h for patients in 60-75kg weight category. 

In patients with acute coronary syndrome who have persistent symptoms despite antianginal treatment, intravenous morphine may be administered in a dose of 2 mg - 4 mg IV stat, followed by 2 - 4 mg every 5 -15 minutes as needed4

Even though morphine is primarily excreted through the liver, in renal dysfunction and CKD, accumulation of its active metabolites (morphine 6 glucoronide) can cause overdose or adverse reactions3. If creatinine clearance is less than 60ml/min, an alternate opioid drug needs to be considered or dosage needs to be reduced to 50 %. If the Creatinine clearance <30ml/min use of morphine should be avoided3,4

Respiratory depression is a serious side effect and requires monitoring in the postoperative patient and because of delayed gastric emptying and reduced peristalsis, constipation, is the other common adverse effect of morphine. Other side effects include central nervous system depression, nausea, vomiting, urinary retention and pruritis2. 

Fentanyl

Fentanyl is a potent synthetic opioid similar to morphine but produces analgesia to a greater extent. It is typically 50 to 100 times more potent than morphine. A dose of only 100 micrograms can produce equivalent analgesia to approximately 10 mg of morphine. It is used as a sedative in intubated patients and for pain relief in patients with renal failure due to its hepatic elimination5. 

Fentanyl comes as an injectable preparation (50 mcg/mL in 2 and 10 ml ampules). Fentanyl infusion is prepared by adding 500mcg Fentanyl (10 ml) to 40 ml NS to make a 10mcg/ml solution in a 50 ml syringe 

Post-operative pain control in non-ventilated patients requires 25-100 mcg IV bolus every 5 mins until pain is relieved or side effects appear. Once pain is relieved a maintenance infusion at 25-50 mcg/hour IV is started as indicated5. (weight based dosing is 0.7-10 mcg/kg/hr depending on severity of pain). 

Fentanyl's side effects include euphoria, confusion, respiratory depression, drowsiness, nausea, visual disturbances and dyskinesia. Fentanyl accumulates in body fat stores and therefore after prolonged use this may delay weaning from the ventilator5.

If creatinine clearance falls to less than 50 ml/min, for continuous infusion the dose needs to be reduced, but generally no dose adjustment is required for infrequent boluses6,7.

Fentanyl trans dermal patches releasing 25 mcg/hr and 50 mcg/hr are available and last 3-7 days. These are used in the HDU and the wards after the patient has been extubated. Doses need to be reduced in patients with renal dysfunction.

NON-OPIOID ANALGESICS

SEDATIVES

Dexmedetomidine

Dexmedetomidine is a highly selective alpha 2- agonist and inhibits central sympathetic outflow by blocking the alpha receptors in the brainstem, thereby inhibiting the release of norepinephrine. It has sedative, anxiolytic, hypnotic, and analgesic effects and decreases the requirement of opioid analgesics. At the same time, it also reduces postoperative nausea and vomiting. Its sedative effect permits tolerance of the endotracheal tube and postoperative ventilation and is routinely used as an infusion in the post operative period except when contraindicated due to bradycardia or AV block. It reduces the incidence of postoperative delirium8 and enhances patient co-operation for Non-invasive ventilation /BiPAP whenever this form of ventilation is used for hypoxemia or hypercarbia after extubation. 

It is also used for patients in the ICU after extubation for sedation, treatment and prevention of delirium, adjunctive analgesia and therapy for insomnia8.

For ICU sedation, the typical dosage range for infusion 0.2 to 0.7 mcg/kg per hour. However, the dose can be increased to 1.5 mcg/kg per hour to achieve the required sedation level. Dosage adjustments for renal or hepatic impairment are not required but should be considered, especially for hepatic impairment7

To achieve the desired effect a bolus of 0.5-1 mcg/kg over 10 mins can first be administered followed by infusion8 Dexmedetomidine for infusion is prepared by adding 200mcg (1ml) of Dexmedetomidine to 49 ml NS for a 4mcg/ml solution in 50 ml syringe.

The most common adverse effects of dexmedetomidine are hypotension and bradycardia but may cause hypertension when given as bolus. It should be used with caution in heart block, bradycardia or heart failure9.

PROPOFOL

Propofol is also commonly used in the postoperative period after cardiac surgery for sedation during mechanical ventilation. It produces sedation without analgesia and in higher doses it is used for total intravenous anaesthesia, Emergence is rapid even after prolonged infusion which enables rapid extubation after stopping the infusion.

Dose is 1- 4 mg/kg/hour by infusion. It is supplied as a 1% solution (10mg/ml in 10 ml and 50 ml vials) and there is no need for dilution9

Propofol can cause hypotension and bradycardia, and occasionally QTc prolongation. It is known to cause hypersensitivity reactions, and rarely after prolonged high dose (>4mg/kg/h for 24h or longer) can cause a propofol infusion syndrome leading to metabolic acidosis, rhabdomyolysis and renal failure 10 

MIDAZOLAM

Midazolam is a short acting benzodiazepine . 

It is given as a bolus of 2 – 5 mg IV for acute severe agitation. For sedation during mechanical ventilation, it used in a dose of  0.01 - 0.1mg /kg/hr by infusion titrated to effect11. Midazolam for continuous IV infusion is prepared undiluted -1mg/ml  in a 50 ml syringe1.

It is to be used with caution in patients with deranged renal or hepatic function when its effect may be prolonged due to increased half-life and accumulation12. In hepatic dysfunction it can trigger or exacerbate hepatic encephalopathy13.

After a prolonged infusion emergence can be delayed and it can lead to cognitive impairment11.

MUSCLE RELAXANTS

Muscle relaxants are generally avoided during postoperative ventilation. When indicated for hypoxic ventilated patients for reducing the oxygen demand, either vecuronium by intermittent bolus or atracurium / cis-atracurium by infusion is used.

Atracurium 

Atracurium is generally preferred as it undergoes spontaneous Hoffman degradation which enables rapid recovery of motor power after stopping the infusion. 

Dose for intubation is 0.5 mg /kg and 0.5 mg /kg /hr infusion  (dose range 11-13mcg/kg/min) for continuous muscle paralysis14. Infusion is prepared undiluted (10 mg/ml) in a 50 ml syringe 10mg/ml. 

Atracurium can cause histamine release causing hypotension14 which is absent with cis-atracurium. However, the duration of action of cis-atracurium is much longer than atracurium which can delay spontaneous motor power recovery, though the residual neuromuscular block can be reversed with neostigmine and glycopyrrolate. Both drugs can be used safely in renal and hepatic impairment15.

Vecuronium

Vecuronium is a steroidal muscle relaxant which is used for intubation in a dose of 0.1mg/kg  and intermittent boluses of 2 mg can be used as required16. 

Recovery of motor power requires a reversal agent, neostigmine in a dose of 50mcg/kg with glycopyrolate 10 mcg/kg15.

A reversal drug preparation of 2.5 mg neostigmine with 0.4 mg glycopyrrolate is available. 

Vecuronium can also be reversed by suggamadex 2-4 mg/kg15.

ADJUNCTIVE AGENTS

Haloperidol 

Haloperidol Is used in the management of postoperative delirium in ICU patients17.

Dose for mild hyperactive delirium is 0.5 to 2.5 mg IV and for severe delirium 5 – 10 mg IV stat can be given. 

In case of inadequate response the drug can be repeated every 30 mins till patient is calm. The maximum dose is 30 mg/day17. It is given as a bolus often combined with promethazine 12.5 mg . 

Haloperidol can cause QTc prolongation which in the presence of other QTc prolonging drugs can precipitate Torsades18

Ketamine

Ketamine is a dissociative anaesthetic which provides excellent analgesia in a subanaesthetic bolus of 0.25-0.5mg/kg (maximum35mg) –followed by low dose infusion of 0.05-0.25mg/kg/hr or, intermittent infusion of 0.1-0.5 mg/kg over 15 minutes11.

It is available as a 50 mg/ml vial of 10 ml and is diluted to a concentration of 10 mg /ml with NS. 

Ketamine can cause hallucinations and delirium which limits its use to patients with severe pain despite opioids19.

NERVE BLOCKS AND REGIONAL ANESTHESIA

In increasing number of centres, regional and peripheral nerve blocks have been introduced as a part of multimodal analgesia after cardiac and thoracic surgery.  It can effectively block pain sensation originating from the site of the surgical incision20.

Traditionally, Intercostal nerve blocks targeting two spaces above and below the thoracotomy incision, posteriorly and anteriorly have been used just prior to thoracotomy closure. Pre-operative, epidural anaesthesia for blocking pain sensation are seldom used now because of associated complications viz. hypotension, hematoma formation, headache from dural puncture, temporary weakness and allergic reactions. 

Current methods used for cardiac surgery include various fascial plane blocks e.gs. ultrasound-guided erector spinae block (ESPB), serratus anterior muscle plane block (SAPB), pectoral muscle blocks (PECS), transversus thoracis muscle plane block (TTMB), and pecto-intercostal fascial plane block (PIFB) 21

PECS, and SAPB are anterolateral approaches that normally cover the lateral region of the chest and are suitable for drains and thoracotomies associated with minimally invasive cardiac surgery22, 23

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