critical care: additional clinical pearls and take home

Critical Care: Additional Clinical Pearls and Take Home Messages

Carolyn M. D’Ambrosio, MS, MDDirector, Harvard-Brigham and Women’s Hospital

Pulmonary and Critical Care FellowshipBrigham and Women’s HospitalAssociate Professor of Medicine

Harvard Medical School

Carolyn M. D’Ambrosio, MS, MD• George Washington University

Medical School• University of Rochester, Strong

Memorial Hospital Residency and Chief Resident

• Yale University School of Medicine Fellowship in Pulmonary and Critical Care

• Associate Professor of Medicine @HMS

• Clinical focus: sleep-disordered breathing

• Research focus: outcomes in OSA

Disclosures

• No financial conflicts with regards to this presentation

• Advisor, Hicuity Health, Inc

• Author, “Comfort the Kid!” book on infant sleep and parent bonding.

• Patent on circadian programming device

• Alcohol is a CNS depressant:– Binds with high affinity to receptors on GABA complex (major

inhibitory neurotransmitter), – tolerance develops easily: more alcohol is needed for same effect.

Sedative and memory impairment

– Inhibits glutamate-induced excitation of the NMDA(N-methyl-D-asparate) receptor: important for being awake. More glutamate receptors are made as an adaptation.

– Cessation of alcohol results in no inhibition of GABA and excess excitation of NMDA

– Dopamine also increased during w/d leading to hyperarousal

Morrow AL, Suzdak PD et al., J Pharmacol Exp Ther. 1988Hoffman PL, Grant KA et al., Ann N Y Acad Sci 1992

Severe Alcohol Withdrawal Syndrome

• Alcohol use is 7th leading cause of death/disability.

• ~ 8 million Americans are alcohol dependent.

• 2-7% of patients admitted for general care likely to develop severe alcohol withdrawal.

Kosten TR, O'Connor PG. N Engl J Med 2003; 348:1786.

Wood E, Albarqouni L, Tkachuk S, et al. JAMA 2018; 320:825.

Facts about Alcohol Withdrawal

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/contents/management-of-moderate-and-severe-alcohol-withdrawal-syndromes/abstract/2

/contents/management-of-moderate-and-severe-alcohol-withdrawal-syndromes/abstract/3

Alcohol Withdrawal Symptoms

Uptodate 20196

Wood E, Albarqouni L, et al., JAMA 20187

Delirium Tremens

• ~5 % prevalence in alcohol w/d

• Definition:– Hallucinations– Tachycardia– Hypertension– Disorientation– Agitation– Fever – Diaphoresis – All in setting of a lack or

reduction of alcohol intake

• Not the same as alcohol hallucinations• All patients have symptoms of Alcohol w/d prior to DT• Risk factors include h/o alcohol w/d seizures, age >30,

longer time since last drink

• Clinical manifestations:– Increased cardiac indices and oxygen consumption– Respiratory alkalosis from hyper ventilation– High ph leads to decreased cerebral blood flow– Hypovolemia– Hypokalemia– hypophosphatemia– Hypomagnesemia (predisposes to dysrhythmias and seizures)

Delirium Tremens

Wood E, Albarquoni L., et al. JAMA 2018Ferguson JA, Suelzer CJ, et al., J Gen Intern Med 1996

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• What is the problem with CIWA-Ar?

– Heavy burden on nursing time

– Large doses of lorazepam increases risk of delirium and respiratory depression

– ICU Treatment of Alcohol Withdrawal

– It cannot be used if the patient is unable to respond to questions.

ICU Treatment of Alcohol Withdrawal

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• Potentiates GABA receptors and antagonizing activity on NMDA

(bzp only affect GABA)

• Anti-epileptic medication

• Ideally give phenobarbital with benzodiazepine to work synergistically on the GABA chloride channel

• Half live is long (53-118 hours)

• Doses: 130-260 mg IV every 15-20 minutes until symptoms are controlled

Phenobarbital

Phenobarbital vs. CIWA-Ar

Tidwell WP, Thomas TL, et al., Am J CCM 2018.

Phenobarbital vs. CIWA-Ar

Tidwell WP, Thomas TL, et al., Am J CCM 2018

Serum levels should be within therapeutic range

The patient may need intubation as it is a sedative, especially in conjunction with bzp (ICU monitoring)

Metabolized by the liver

Some drugs alter the serum concentration

Phenobarbital

Brotherton AL, Hamilton EP, et al., Pharmacotherapy 2016

Propofol

Benefits

Agonist of GABA and reduces gulatamine action on NMDA

Requires intubation

Anti-epileptic properties

Harm

Hypotension

Longer duration of Mechanical Ventilation

Longer length of stay

Ferenchak TA. J Addict Nurs. 2017

Dexmedetomidine

Benefit

Alpha2 adrenoceptor agonist

Sedation without respiratory depression

Reduces amount of bxp

Decreases mech vent, ICU LOS and hospital LOS

Harm

Hypotension

Bradycardia

Cost $$$

• Summary

– Best treatment is prevention/early detection

– Bzp first line therapy for all types of alcohol w/d and may require massive doses

– Consider use of phenobarbital either alone or in conjunction with bzp ( some places use it alone)

– For intubated patients, propofol works well

– Remember supportive care IVF, thiamine, glucose, MVI, etc.

Alcohol Withdrawal in Critically ill Patients

• Intensive Insulin Therapy vs. Conventional

– The NICE-SUGAR study

– RCT of 6104 patients in ICUs

– IIT (goal BG 81-108 mg/dl) vs conventional (BG <180mg/dl)

– Primary endpoint death from any cause at 90 days.

• The NICE-SUGAR Study Investigators. N Engl J Med 2009

Hyperglycemia in Critical Illness

The NICE-SUGAR Study Investigators. N Engl J Med 2009;360:1283-1297.

Data on Blood Glucose Level, According to Treatment Group.

The NICE-SUGAR Study Investigators. N Engl J Med 2009;360:1283-1297.

Probability of Survival and Odds Ratios for Death, According to Treatment Group.

• Death from CV causes more common in IIT

• No difference in median LOS or ICU LOS

• IIT had more severe hypoglycemia (< 40 mg/dl)

• Overall increased mortality in IIT group after controlling for many confounders (27.5 % vs 24.9%)



• CORIITSS trial (Corticosteroids and Intensive Insulin Therapy for Septic Shock)

– Patients who were on corticosteroids randomized to IIT vsconventional

– No difference in mortality, ICU LOS, ventilator free days or vasopressor free days.

• CORTIISS study Investigators, JAMA 2010


• VISEP trial (Volume Substitution and Insulin Therapy in Severe Sepsis)

– Multicenter, med/surg ICU

– Compared IIT to conventional, also different volume resuscitation approaches

– IIT arm stopped early d/t high rate of hypoglycemia (12.1%) and serious adverse events (10.9%)

• Brunkhorst FM, et al., NEJM 2008


• Hypoglycemia…why is it bad?

– Seizures

– Brain damage

– Depression

– Cardiac arrhythmias

– Death• Brunkhorst FM, et al., NEJM 2008


• Preiser JC, et al., Intensive Care Med 2009

• Krinsley JS, Grover A., Crit Care Med 2007


• Summary:

– To date, there is no universally accepted insulin regimen for glucose control in critically ill patients

– Hyperglycemia (BG >180-200 mg/dl) associated with poor outcomes

– IIT (BG goal 80-110 mg/dl) increases risk of hypoglycemia, possibly mortality

– BG 140-180 mg/dl associated with lower mortality, fewer episodes of hypoglycemia.


• Early source identification and control

Surviving Sepsis Guidelines 2016

• Early volume resuscitation: crystalloid

Semler MW, et al. , NEJM 2018

Sepsis

• ARDS: – TV 4-8 ml/kg of PBW

– plateau pressures < 30 cmH2O

– Higher PEEP vs lower

– Prone positioning helpful in some patients

Fan E, et al. ATS/ERS/ICM/SCCM guidelines 2017.

Mechanical Ventilation

Pain, Agitation, Delirium, Immobility, Sleep

Pain:

Assess with validated tools, manage with opioids as needed but consider pharmacologic and non-pharmacologic adjuncts. Protocols work.

Agitation:

Light better then deep sedation. If infusion, either daily interruption or nurse-driven targeted protocol.

Delirium:

Assess regularly. Pharmacologic prevention not recommended. Prevention best.

Immobility:

Rehab/mobilization is safely done and recommended for most ICU patients.

Sleep:

ICU patients are known to sleep poorly and this may have consequences. Non-pharmacologic intervention recommended; no pharmacologic intervention is proven.

Questions?

critical care: additional clinical pearls and take home

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