Respiratory Depression and Considerations for Monitoring Following Ophthalmologic Surgery

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Respiratory Depression and Considerations for Monitoring Following Ophthalmologic Surgery Athir Morad, M.D. Division of Neurocritical care Departments of Anesthesiology/ Critical Care Medicine and Neurology The Johns Hopkins University School of Medicine morada@jhmi.edu

Disclosures I have no financial relationships to disclose. I will not discuss off label use or investigational use in my presentation.

Learning Objectives 1. To discuss the impact of sedation and General Anesthesia (GA) on postoperative respiration. 2. To review the efficacy of postoperative monitoring in capturing respiratory depression.

Postoperative Opioid-induced Respiratory Depression: A Closed Claims Analysis Lee et al. Anesthesiology. 2015

Risk Factors 33% involved multiple prescribers 34% received concurrent non-opioid sedatives 31% received inadequate assessment or response Lee et al. Anesthesiology. 2015

Additional Observations Discovery within 2 hours: 42% 15 minutes: 16% Somnolence was present in 62% of patients 2/3 of patients were obese 1/4 of patients had either diagnosed or suspected OSA based on Stop Bang criteria. Lee et al. Anesthesiology. 2015

STOP Questionnaire to Screen for OSA 1. Snoring Do you snore loudly (louder than talking or loud enough to be heard through closed doors)? Yes No 2. Tired Do you often feel tired, fatigued, or sleepy during daytime? Yes No 3. Observed Has anyone observed you stop breathing during your sleep? Yes No 4. Blood pressure Do you have or are you being treated for high blood pressure? Yes No 5. BMI BMI more than 35 kg/m2? Yes No 6. Age Age over 50 yr old? Yes No 7. Neck circumference Neck circumference greater than 40 cm? Yes No 8. Gender Gender male? Yes No High risk of OSA: answering yes to three or more items Low risk of OSA: answering yes to less than three items Chung et al. Anesthesiology. 2008

88% of events occurred within first 24 hours of surgery Lee et al. Anesthesiology. 2015

Why did12% of events occur after POD1? Preop N1 N3 N5 N7 Modified. Chung et al. Anesthesiology 2014.

https://nei.nih.gov/eyedata/cataract

https://nei.nih.gov/eyedata/glaucoma

Scott et al. J Pharmacol Exp Ther. 1987

Joosten et al. Chest. 2017

Association between OSA and Ophthalmologic Disease Huon et al. Sleep Breath. 2016

Pretest Opioids induce respiratory depression.

Pretest Pulse oximetry reliably captures episodes of respiratory depression in patients recovering from ophthalmologic surgery.

Pretest Respiratory depression increases measured End Tidal CO2.

Pretest End Tidal CO2 measurement provides reliable detection of opioid induced respiratory depression.

Myth Patients do not experience intense pain following intracranial surgery. Surgical manipulation of the brain parenchyma per se is not painful. Dunbar et al., Anesth Analg. 1999

FACT: 2/3 patients report moderate to severe pain Number with Pain (%) 100 80 60 40 20 Pain > 0 Pain > 3 Pain > 6 0 1 2 Postoperative Day (At Rest/With Movement) Gottschalk et al., J. Neurosurgery. 2007

How was the pain treated? Percentage of Patients Treated With Opioids P value 1 st Postoperative Day 50.4 0.002 2 nd Postoperative Day 32.6 0.015 Gottschalk et al., J. Neurosurgery. 2007

How was the pain treated? Percentage of Patients Treated With Opioids P value 1 st Postoperative Day 50.4 0.002 2 nd Postoperative Day 32.6 0.015 Potentially toxic doses of acetaminophen were ordered: POD1: 42% POD2: 33% Gottschalk et al., J. Neurosurgery. 2007

Morad et al., J Neurosurg. 2009

Supratentorial Craniotomy Pain 6 Pain scores (0-10) 5 4 3 2 PRN PCA 1 0 0 5 10 15 P= 0.026 Time from Neurosurgical ICU admission (hrs) Morad A, et al. J Neurosurg 2009.

But is it SAFE? Vorenkamp et al., J Neurosurg. 2009

Major Safety Concerns Regarding Opioids Hypoxia Hypercarbia Sedation

Influence of Opioids on Sedation Hammoud et al., Pain. 2009 modified

A Mechanism for Opioid Induced Sedation µ receptor activation hyperpolarizes cholinergic neurons projecting from the basal forebrain to the prefrontal cortex. Osman et al., Anesthesiology. 2005

Titration of Opioids to Sedation Sufficient Analgesia Lentschener et al., Anesth Analg. 2007

Relation between CO2 and Intraocular Pressure Kielar et al. Invest Ophthalmol Vis Sci. 1977

Carbon Dioxide Production Net reactions for glycolysis of glucose, oxidative decarboxylation of pyruvate, and Krebs cycle. 2015

Carbon Dioxide Signaling- Central Chemoreceptors Arterial Blood CSF Medullary Arterial Blood Chemoreceptors CO2 B B B Carbonic Anhydrase HCO 3 - H+ (decreased ph) + + B B B CO2

Central Regulation of Breathing pre-bötzinger complex (rhythm) Respiratory centers of the brain. 2013

Central Regulation of Breathing pre-bötzinger complex (rhythm) Respiratory centers of the brain. 2013

Peripheral Regulation of Breathing Glossopharyngeal Nerve (CN IX) Vagus Nerve (CN X) Respiratory centers of the brain. 2013

Effect of Opioids on Breathing pre-bötzinger complex (rhythm) Glossopharyngeal Nerve (CN IX) Vagus Nerve (CN X) Respiratory centers of the brain. 2013

Influence of Oxygen on Respiratory Drive Loeschke et al., Arch Ges Physiol. 1958 modified

Influence of PaCo2 on Ventilation Pattinson et al., Br. J. Anaesth. 2008 modified

Influence of Opioids on Ventilation Pattinson et al., Br. J. Anaesth. 2008 modified

Relation between PaCO2 and PAO2 PAO2 FiO2 (P ATM -ph2o) - PaCO2/RQ 100 mmhg 0.21(760mmHg-47 mmhg)-40 mmhg/0.8 PAO2 at CO2 40mmHg 150-50=100 PAO2 at CO2 of 60 mm Hg 150-75=75

SaO2 Monitoring Changes in SpO2 (closed) and EtCO2 (open) during hypoventilation in patients receiving FiO2 of 21%, 25%, and 30% Fu et al., Chest. 2004

Effect of Remifentanil on Ventilation during Normoxia and Hyperoxia Niesters et al., Br. J. Anaesth, 2013

Previous Estimates of Respiratory Depression (Intermittent Assessment) Cashman et al. Br J Anaesth. 2004

Incidence of Respiratory Depression (Measured Continuously) Incidence of bradypnea Respiratory rate less than 10 br/min lasting for greater than 2 minutes: 58% Incidence of hypoxia Saturations below 90%: 21% Overdyk et al., Anesth Analg. 2007

Incidence of Respiratory Depression (Measured Continuously) Incidence of bradypnea Respiratory rate less than 10 br/min lasting for greater than 2 minutes: 58% (1.2%) Incidence of hypoxia Saturations below 90%: 21% (11.5%) Overdyk et al., Anesth Analg. 2007

Mitka. JAMA. 2015

PCA-SAME Study: Post Craniotomy Analgesia- Safety Monitoring with EtCO2 Primary Objective: To determine the safety of opioid analgesic therapy in male and female adult post- supratentorial craniotomy patients randomly assigned to receive either IVPCA or IV PRN opioids as defined by Respiratory rate < 10 breaths per minute [bpm] for greater than 2 minutes measured non-invasively by side stream capnography.

PRN PATIENT O2 Sat HR CO2 RR Doses Morad et al., American Society of Anesthesiologists. 2015

PCA PATIENT O2 Sat HR CO2 RR Doses Morad et al., American Society of Anesthesiologists. 2015

Morad et al., American Society of Anesthesiologists. 2015

Sasaki et al., Anesthesiology. 2013

Effect of Opioids on Breathing

Post Test Opioids can induce respiratory depression.

Post Test Pulse oximetry reliably captures episodes of respiratory depression in patients recovering from ophthalmologic surgery.

Post Test Respiratory depression increases measured End Tidal CO2.

Post Test End Tidal CO2 measurement provides reliable detection of opioid induced respiratory depression.

Summary 1. Opioids, alone and in combination with other sedatives, induce respiratory depression by decreasing respiratory drive AND obstructing upper airway motor tone. 2. Continuous monitoring for respiratory depression is better than intermittent assessment. 3. Supplemental oxygen masks opioid induced respiratory depression. 4. End-tidal CO2 monitoring in non-intubated patients is inadequate in detecting opioid induced respiratory depression. 5. Preoperative patient screening and postop monitoring protocols are critically important.

Acknowledgements My research participants, our NCCU staff and Allan Gottschalk Beth White Myron Yaster Marek Mirski Srinivasa Raja Lauren Berkow Christina Miller Robert Stevens Brad Winters Jon Weingart Rafael Tamargo The Blaustein Foundation