Sedation & Paralytic Therapy in the ICU Leanna R. Miller, RN, MN, CCRN-CSC, PCCN-CMC, CEN, CNRN, NP Education Specialist LRM Consulting Nashville, TN

Objectives Identify the purpose for pain, sedation, & paralysis management in the ICU patient Analyze and compare assessment methods for determining appropriate pain, sedation & paralysis management. Recognize and apply the different pharmacotherapeutics used in the ICU for pain, sedation, & paralysis.

Goals of Critical Care Management Save the salvageable and relieve suffering Peaceful & dignified death without prolonging life Curative therapy should not supplant palliation of pain Use of state-of-the-art interventions Aggressive & fast paced therapy according to need Quality pain management mandatory for all patients

Consciousness/Sedation The Balance of Analgesia, Sedation, and Paralytics to promote comfort

What is Sedation? Several Clinical Definitions: process of establishing a state of calm promoting a sense of well-being reduction of anxiety and agitation through the use of pharmacotherapy Sedation is NOT analgesia 80% of Doctors and 40% of ICU nurses answered that benzodiazepines provided analgesia (1990s)

Pathophysiology Response of Stress and Anxiety Cardiovascular Release of systemic epinephrine and norepinephrine Elevated HR and BP Increased cardiac O2 demand Decrease end-organ perfusion Endocrine Release of Cortisol, Glucagon, Glucose Hyperglycemia

Pathophysiology Response of Stress and Anxiety Neurological Increased response and activation of peripheral pain fibers Increased sensation to pain Release of neurotransmitters in the brain Pain Agitation Delirium

Pathophysiology Response of Stress and Anxiety Immune Increased levels of prostaglandins, cortisol, glucose, cytokines, Increase anti-inflammatory response Decrease wound healing SIGNIFICANT STRESS IN THE ICU PATIENT OVERALL CAUSES ORGAN ISCHEMIA AND DECREASED HEALING

Analgesia Clinical Definition: The absence of pain through the use of pharmacotherapy Acute and chronic pain in the ICU activates the stress response Patients with analgesia can still experience anxiety

Its essentially a maintenance therapy” PAIN THERAPY - Myth “One size fits all or Set and forget therapy. Its essentially a maintenance therapy”

Truths Majority of ICU patents suffer moderate/severe pain 40% are delirious & cannot communicate 50% are either physically/emotionally distressed 10-20% have no hopes of cure --- end-of-life in ICU Balance between pain relief & maintaining alertness Multidisciplinary team for multimodal therapies.

Pain in ICU Repeated episodes of acute pain localized Surgery/tissue inflammation immobility catheter/ apparatus discomfort/ nasogastric & orogastric tubes endotracheal intubation/ suctioning/ chest tubes phlebotomy/vascular access/physiotherapy routine turning & positioning the patient

Types of pain in ICU Somatic – most common –localized  opiates Visceral – cramping & colicky  anticholinergics Neuropathic – burning / shooting  antidepressants Mixed type  combination therapy Sustained or chronic pain of varying degrees

Inherent Problems difficult to differentiate due to lack of communication untreated pain affects all body systems synergistic effect of pain on anxiety, depression, sleep all modalities are unpredictable & have adverse effects pain therapy to be tailored to individual needs.

Assessment of pain in ICU Pain as the 5th vital sign- requires frequent evaluation Cognitive impairment/delirium markers Behavioral (facial, FACS) Physiological (BP, HR, RR) Creative assessments (teaching hand movements, blinking Subjective quantification (numeric/graphic scales –W-B faces)

Assessment of pain in ICU

Treatment of Pain treatment of perceived & prevention of anticipated pain Opiates – principal agents in ICU - potent / lack ceiling effects - mild anxiolytic & sedative - relieves air hunger & suppresses cough in respiratory failure - improved patient – ventilator synchrony - effective antagonist – naloxone lack amnesic effects /additional sedatives required

Treatment of Pain adjuvant / non-pharmacological / multimodal therapies Simple Relaxation – must begin preoperatively Jaw relaxation Progressive muscle relaxation Simple imagery Music (either patient – preferred or “easy listening” are effective in reducing mild to moderate pain Complex Relaxation – must begin preoperatively Biofeedback imagery

Causes of Pain in the ICU? Routine care: Suctioning, turning, Surgical Incisions Lines/Chest tubes

The Messengers of Pain Bradykinin, Prostaglandins, Cytokines Histamine Direct tissue damage stimulates pain fibers Local Inflammatory mediators Bradykinin, Prostaglandins, Cytokines Tissue Injury Histamine Serotonin TNF

WHY IS THIS IMPORTANT?

Common Analgesic Drugs in the CVICU Dose Onset Peak Duration Morphine Renal 1 - 4 mg 5 min 20 min 4 - 5 hrs Fentanyl Liver 25 – 100 mcg 1 - 2 min 3 - 5 min 30 - 60 min Remifentanil Plasma .5 – 40 mcg/kg/h <1 min 3 - 10 min Dilaudid .25 – 2 mg 10 - 15 min 15 - 30 min 2 - 3 hrs Toradol 15 – 30 mg Immediate 1 - 3 min 6 - 8 hrs

A Focus on Morphine First narcotic to be used Narcotic standard Relies on good kidney function for excretion Stimulates mast cells to release histamine Itching Rash Hypotension Acute Asthma episode No longer used frequently due to newer drugs

A Focus on Fentanyl 100x stronger then Morphine Fastest metabolizing narcotic used in the CVICU Chest Wall Rigidity can cause shortness of breath and difficulty weaning occurs most often with high IV bolus doses Decreases BP and HR

A Focus on Remifentanil Newest synthetic narcotic derived from Fentanyl Eliminated by plasma esterases Metabolism not dependent on liver or kidney function Elimination not dose dependent Advantages Organ independent metabolism Lack of accumulation Provides analgesia and sedation in ventilated patient Disadvantages Expensive Severe withdrawal Rebound hyperalgesia

A Focus on Toradol Is a potent IV/IM NSAID Decreases sternal incision pain and inflammation Like many NSAIDs can be nephrotoxic Know your patients BNP and Creatinine Can cause GI bleeding Usually not given if the patient is… Age >75 Elevated creatinine Chest tube bleeding Low platelets

Sedation in ICU used in the agitated, ventilated & for procedure discomfort to avoid self extubation & removal of catheters NM blockade mandates analgesia & sedation control of pain before sedation all have side effects – dose dependent analgesics are not sedatives/ Sedatives are not analgesics

Common Sedatives in the ICU Drug Dose Onset Peak Duration Ativan Liver .5 - 2mg 5 min. 60-90 min 6 - 8 hrs Versed 1 - 2mg 1.5 - 5 min Rapid 2 - 6 hrs Propofol Liver* Starts at 25 mcg/kg/min <40 sec. 3-5 min 10 - 15 min Precedex Plasma .2-.7 mcg/kg/hr (3mcg/kg/hr) 15 - 30 min 30 min 60 - 120 min Ketamine 2 – 7 mcg/kg/min 30 s 1 min 5 - 10 min

A Focus on Precedex Only sedative used that does not cause respiratory depression Patients can be weaned and extubated while on Precedex Usual titration range 0.2 – 0.7mcg/kg/hr MD order >0.7mcg/kg/hr Titrate by 0.1-0.2mcg/kg/hr q30-45min Can cause SEVERE bradycardia and hypotension Very expensive!

A Focus on Ketamine dissociative anesthetic  light sedation & amnesia used as an adjunct for patients with uncontrolled pain or inadequately sedated rarely used in the CVICU due to myocardial depressant properties monitor for hallucinations and vivid dreams

Assessment of Pain and Sedation

Sedation scoring systems Assess levels to vary according to course of ICU stay Observational scales - 4 levels – min, mod, deep, GA Addenbrooke sedation scale 0-7 (vocal, tracheal suction) Ramsay sedation scale 1-6 (vocal, glabellar tap)--aim for 3-4 Direct information- ideal to assess analgesia & sedation BIS – for deep sedated & paralyzed

RASS ASSESSMENT +4 Combative, violent, danger to self/staff +3 Very agitated, pulls lines, tubes, aggressive +2 Agitated frequent non-purposeful movement, fights the vent +1 Restless / Anxious but not aggressive or vigorous 0 Alert and calm -1 Drowsy, not fully alert but can stay awake, eyes open to voice for >10sec -2 Light sedation, wake and makes eye contact for < 10 sec -3 Moderate sedation, moves/opens eyes to voice but no eye contact -4 Deep sedation, no response to voice but moves or opens eyes to physical stimulation -5 Unarousable, no response to stimuli

BIS monitor

BIS Monitoring

BIS Monitor BIS monitor utilizes EEG waveforms. reading is monitored from the patient’s forehead. excessive muscle activity can interfere with EEG detection

Bispectral Index BIS – an attempt to objectively monitor patients sedation processed EEG measurement that gives a score to help determine the patient’s response to sedation useful to help titrate medication proper sensor placement is key to accurate monitoring

Sensor Application Apply sensor on forehead at angle Circle #1: Centered, 2 inches above nose Circle #4: Directly above eyebrow Circle #3: On temple, between corner of eye and hairline Press around the edges of each circle to assure adhesion Press each circle for 5 seconds

BIS Placement Make sure the forehead is clean and dry! Label the sensor with date/time Replace sensor every 24 hours and PRN

BIS Monitor implement BIS monitoring on all patients with paralytic drips infusing purpose of BIS monitor is to provide a direct measurement of the SEDATIVE effects on the brain. goal for BIS Monitoring will be 40 – 60. studies have indicated that this is a safe range for no memory recall.

BIS Monitoring

Troubleshooting the BIS If the BIS increases suddenly or is higher than expected: Consider: Is the sedative dose sufficient? Is there an increase in stimulation? When was the last analgesic given? Is the patient adequately paralyzed? TOF? Is the patient having a seizure

Troubleshooting the BIS If the BIS decreases suddenly or is lower than expected: Consider: Has there been a decrease in stimulation or increase in sedation/analgesia? Is the patient significantly hypothermic? Has there been a sudden significant drop in BP?

BIS Monitoring Always consider the overall picture of the patient Ex: if nothing significant has changed with patient and BIS number suddenly reflects very different readings then fall back to your overall assessment of the patient

REMEMBER! Look at the BIG PICTURE! Do Not Forget You are treating a patient not just the number

“Sedation Vacation” Assess for daily awakening Exclusions Increased ICP Neuromuscular blockade Significant ventilation support CABG, immediate post-op

“Sedation Vacation” Is patient awake and calm? SAS 3 – 4 RASS 0 to -1 If no, restart sedation @ ½ previous dose If yes, proceed to spontaneous breathing trial (SBT)

“Sedation Vacation” Assess for SBT Calm & co-operative Hemodynamically stable PEEP < 8 FiO2 < 0.60 pH > 7.34 SpO2 > 90%

“Sedation Vacation” SBT Termination Criteria RR > 35/min for > 5 minutes SpO2 < 90% for > 2 minutes New ectopy HR change 20% from baseline BP change 20% from baseline Accessory muscle use Increased anxiety/diaphoresis

“Sedation Vacation” Conduct SBT for 1 minute Mode CPAP PEEP = 0 PS @ least 5 – 10 FiO2 unchanged

Paralytics in the ICU Paralysis – the loss of voluntary muscular function due to the administration of a paralytic Neuromuscular Blockade Agent (NMB) – Drugs that obstruct transmission of nerve impulses to the muscle Neuromuscular Blockade agents DO NOT BLOCK THE TRANSMISSION OF PAIN!!!!

Paralytics in the CVICU Sedation and Analgesics must always be given FIRST Must use sedatives with an Amnesic affect Benzodiazepines (VERSED) High dose Propofol Paralytics are always given LAST

Why Do We Paralyze? Decreases O2 demand ARDS Prevent Patient-Ventilator dysynchrony VDR ventilators BiVent Prevents Shivering in hypothermia patients Shivering increases O2 demand Raises patients temperature Open chest

Checklist for chemical paralysis Must be adequately sedated first before paralytic administered Must have anxiolytic drip that has amnesic properties Must have analgesic drip infusing Must have lubrication for eyes/eye bubbles

Common CVICU Paralytics Drug Dose Onset Peak Duration Vecuronium .08 - .1 mg/kg 1 min 3-5 min 15-25 min Pancuronium .04 -.1 mg/kg 30-45 sec 3-4 min 35-65 min Succinylcholine .6 mg/kg 30-60 sec 1-2 min 4-10min Nimbex 3 mcg/kg/min 2-5 min 25-44 min

A Focus on Vecuronium A non-depolarizing NMB Will NOT increase K+ Full recovery from paralytic 25-40min Frequently used in the CVICU for intubation or as a bolus drug before Nimbex Rarely used as a drip in the absence of Nimbex 0.8-1.2mck/kg/min

A Focus on Succinylcholine A depolarizing NMB Can increase K+ ~ 0.5-1mEq/L KNOW YOUR PATIENTS K+ before administering Does your patient have any renal disease? Metabolized by plasma cholinesterase Very rapid metabolism ~5min Does not rely on kidney or liver function

A Focus on Nimbex Is our primary titrating NMB used in the CVICU Is also metabolized in the blood Standard dose is 3mcg/kg/min Titrate range: 0.5-5mcg/kg/min Metabolism ~45min Changes with hypothermia?

Successful Paralysis: How do we know? Assessment Movement Spontaneous Breaths Peripheral Nerve Stimulator

Peripheral Nerve Stimulators Peripheral Nerve Stimulator – A device that delivers a determine electrical current to create a muscular contraction Used to determine the amount of neuromuscular blockade a patient has An increase in NMB will show a decrease response to a peripheral nerve stimulator at a set current

Train of Four Train of Four – 4 consecutive impulses generated from the peripheral nerve stimulator resulting in 4 muscular twitches # of twitches seen = degree of NMB No blockade – 4 twitches Total blockade – 0 twitches GOAL IS 1-2 TWITCHES Increase drip by 10% if >2 twitches Decrease drip by 10% if <1 twitch

Train of Four: Facial Nerve Place one electrode on the face at the outer canthus of the eye (positive/red electrode) Place the second electrode 2 cm below and parallel with the tragus of the ear (negative/black electrode) Watch and feel for facial nerve contraction

Train of Four: Ulnar Nerve

Train of Four Must have 2x baseline TOFs before starting NMBs Ulnar nerve is more preferred but facial nerve is easier to see/assess Use alcohol pad to wipe clean and dry the skin before applying electrode Electrodes must be changed 24 hrs Possibly inaccurate in hypothermia patients…

Helpful tips for TOF If checking the thumb – ensure the leads are placed on the ulnar side of the arm(this is where the nerve lies) Be careful with applying maximum MA’s when leads are placed on the face – this can lead to burns/scarring Check your battery Change your electrodes q24h

Putting it all Together start BIS Monitoring get a Baseline TOF on two locations start Sedation and Analgesic Drips titrate medication up until BIS 40-60 bolus paralytic start paralytic drip check TOF q30min until 1-2 twitches monitor TOF and BIS and titrate drips to endpoints

***** CRUCIAL POINT ****** Prior to the administration of any paralytic agent - sedation MUST be administered first. If paralytic will be continued as an infusion, sedation MUST also be continued. Sedation MUST be a drug that has amnesic properties.

Drugs that have amnesic effects Benzodiazepine class Examples: Versed Propofol (in high doses) dose will be individual to patient

Intravenous Medicines commonly used in CVICU SEDATION Ativan * Versed * Propofol ** Precedex *** * Amnesic properties ** Amnesic in high doses only *** DOES NOT have amnesic properties ANALGESIA Morphine Fentanyl Dilaudid Toradol

Case Study You are caring for a patient that has an open chest, they are on a Nimbex, Fentanyl & Versed gtts: VS’s: BP 160/90 HR 128 Vent Settings: SIMV 12, TV 450, PEEP 5, PS 10, Spontaneous RR 12, 02 saturation 98%, TOF 2/4 Is anything wrong here?

Case Study Patient has open chest, Nimbex, Fentanyl & Versed gtts: VS’s 105/68 HR 80 Paced Vent settings: SIMV 12, TV 600, PEEP 5, PS 10, Spontaneous RR 16 TOF 2/4 Is anything wrong here?

Case Study Patient has open chest, has experienced excessive blood loss through chest tubes, Nimbex & Propofol gtts(5 mcg/kg/hr) VS’s BP labile 70’s to 100’s systolic HR 80’s paced Vent settings: SIMV 12, TV 400, PEEP 5, PS 5, Spontaneous RR 14, 02 saturation 98% TOF 0/4 Is anything wrong here?

SCCM task force recommendations Benzodiazepines most popular for sedation Short term sedation Midazolam <3h (amnesic/ hypotension) propofol – infusion syndrome/ pancreatitis Long term – lorazepam <20h /diazepam>96h (not for infusion) Delirium – haloperidol - neuroleptic syndrome/ torsade pointes Antagonist- flumazenil 0.2mg-1mg (withdrawal seizures)

ReCap of Key Points Sedation: Analgesia: Paralytics: Patient may still experience pain, goal is anti-anxiety/ – relaxation, goal is usually to give amnesia Analgesia: Used to treat pain, no anti-anxiety properties Paralytics: Used to decrease skeletal muscle movement, imperative that amnesic drugs be used in combination with analgesic meds, MUST sedate before paralyzing

ReCap of Key Points BIS Monitor: Peripheral Nerve Stimulator: Used to strictly assess patient’s sedation level Goal is 40-60 Peripheral Nerve Stimulator: Used to strictly assess patients paralytic state TOF goal is 1-2/4

Putting it all Together start BIS Monitoring get a Baseline TOF on two locations start Sedation and Analgesic Drips titrate medication up until BIS 40-60 bolus paralytic start paralytic drip check TOF q30min until 1-2 twitches monitor TOF and BIS and titrate drips to endpoints

Final Thoughts give sedation/analgesia before paralytics BIS assess for sedation TOF assess for adequate NMB If in doubt it never hurts to ask!

References Gelinas C. Management of pain in cardiac surgery ICU patients: have we improved over time? Intensive Crit Care Nurs. 2007;23(5):298-303. Girard TD, Shintani AK, Jackson JC, et al. Risk factors for post-traumatic stress disorder symptoms following critical illness requiring mechanical ventilation: a prospective cohort study. Crit Care. 2007;11(1):R28. Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30(1):119-141. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298(22):2644-2653.