Anaesthesia

Small Group Discussion

Festejo, Katrina MarieHo, Beverly Lorraine

Hugo, LarimerIgnacio, Anna lore

Gen Data• Vicky Bragais• 59/F• Married• R-handed• Roman Catholic• Manila

Chief Complaint• Low back pain

History• 2 years PTA– Low back pain, hematuria,

dysuria, fever• No chills, lithuria

– Consulted at Martinez Memorial Hospital• A> Renal Calculi R>L• P> Surgery

– Patient opted to seek 2nd opinion but was lost to follow up until…

History• 1 year PTA– Still with hematuria, low back pain– No lithuria, no fever, no chills– Now with crampy abdominal pain

VAS 9/10– Rushed to Martinez Hospital• UTZ: Non-obstructing nephrolithiasis,

bilateral• U/A: (+) sugar, RBC 10-15/hpf, PMN

TNTC, EC occ, Bacteria many– Again, advised surgery but refused

History• 1 month PTA– Persistence and progression

prompted consult at Chinese General Hospital• CT Stonogram: Bilateral staghorn

calculi with hydronephrosis R>L– Admitted with the following

working impression• Urosepsis secondary to Staghorn

Calculi– Discharged improved after 4 days

History• Few days PTA– Recurrence of low back pain

prompted consult at the Philippine General Hospital DFCM Clinic

Review of Systems• (-) headache• (-) BOV• (-) nausea/vomiting• (-) anorexia• (-) weight loss• (-) cough or colds• (-) chest pain• (-) dyspnea• (-) orthopnea• (-) constipation• (-) muscle or joint pains• (-) polyuria, polydipsia, polyphagia

Past Medical • (+) Rheumatoid Arthritis, 2009–Maintained on pain meds PRN

basis

Family Medical• (+) Rheumatoid Arthritis –

father

Personal Social• Married to fellow retiree• Former school teacher• No vices

Physical Examination• Lying on a stretcher, conscious,

coherent, oriented, not in cardio-respiratory distress

• Vital signs stable– BP 130/80 mmHg– HR 90 – RR 18– Temperature

Physical Examination• HEENT: anicteric sclerae, pink palpebral

conjunctivae, no cervical masses or lymphadenopathy

• Chest and Lungs: symmetric chest expansion, no deformities, no retractions, clear breath sounds

• CVS: adynamic precordium, distinct heart sounds tachycardic, regular rhythm, no murmurs

• Abdomen: flabby, no direct tenderness, (+) CVA tenderness on R>L

• Extremities: full and equal pulses, no cyanosis, no clubbing, no edema

Neurologic Exam• GCS 15, coherent, cooperative• Oriented to time place and

person• No sensory and motor deficit

Assessment• Nephrolithiasis, bilateral

Plan• SAPOD Clearance• Surgery:– Pelvolithotomy, L– Radial nephrolithotomy, R

Course

Day 1 •Admitted•Referred to SAPOD

Day 2 •SAPOD cleared

Day 3 •OR Schedule

Anaesthesia Pre-op• NPO 6 hours PTOR• IVF D5NR 1L x 8 hours• Meds 1 hour PTOR– Nalbuphine 10mg IM – Promethazine 25mg

Anaesthesia Intra-op• XT

– LLDS, SAAS– Local infiltration with lidocaine 2%– LP at L4-L5 using TNG18 2 attempts– 1st attempt (+) CSF– 2nd atttempt (+) LDLTH @ L3-L4 (-) blood (-)

TD• X2– Fentanyl 500, Propofol 10, Atracurium 30s

• Intraoperatively, NO hypotensive episodes, MINIMAL blood loss

Anaesthesia Post-op• Ketorolac 30mg IV Q6 hours x 4

doses• Morphine sulfate 0.03%

10cc/epidural Q12 hours

At the PACU• Received with stable vital signs

– BP 110/70, HR 88, RR 18, UO>0.5cc/hr• 1 hour post-op

– BP 110/70, HR 90, RR 18, UO>0.5cc/hr• 2 hours post-op

– (+) vomiting of yellowish clear liquid– BP 110/80, HR 92, RR 18, UO > 0.5cc/hr– Patient observed, reassured– (-) recurrence of vomiting

• The rest of her PACU stay was unremarkable

Vomiting

Pathophysiology• coordination of the respiratory,

gastrointestinal and abdominal musculature

• vomiting center: lateral reticular formation – in close proximity to the nucleus

of the solitary tract in the brain stem

– access to the motor pathways that are responsible for the visceral and somatic output involved in vomiting

Vomit Detectors• gastrointestinal tract (GIT)

– vagus nerve • mechanoreceptors - muscular wall of the gut,

activated by contraction and distension of the gut • chemoreceptors - mucosa of the upper gut,

sensitive to noxious chemicals

• chemoreceptor trigger zone (CTZ)– area postrema

• U-shaped structure a few millimeters long located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle

• Outside BBB and CSF barrier: can be activated by chemical stimuli received through the blood as well as the cerebrospinal fluid

CNS (cerebral cortex, labyrinthine, visual, vestibular apparatus)

Oropharynx

Mediastinum

Peritoneum

Genitalia

CTZArea Postrema

GIT

Receptors• vomiting center and vestibular

nuclei: cholinergic receptors• area postrema: dopamine (D2),

opioid and serotonin (5HT3) receptors

• nucleus tractus solitarius: enkephalins, histaminic (H1), muscarinic cholinergic and NK-1 receptors

• dorsal motor nucleus of the vagus nerve: NK-1 receptors

Risk Factors• Patient related factors– female– history of PONV or motion sickness– non-smoking status– High levels of anxiety and

postoperative pain, (pelvic or visceral origin)

Risk FactorsSURGERY - Adults:• intra-abdominal

surgery• major

gynecological surgery

• laparoscopic surgery

• breast surgery• neurosurgery• eye and ENT

surgery

SURGERY - Pediatrics: • Strabismus• adenotonsillectomy• hernia repair• orchidopexy• penile surgery • middle ear

procedures

Risk factors• Anesthesia related risk factors:– volatile agents– nitrous oxide– opioids– high doses of neostigmine (>2.5

mg) for the reversal of neuromuscular blockade

Risk Scoring Systems• Palazzo and Evans

– logit postoperative sickness = -5.03 + 2.24 (postoperative opioids) + 3.97 (previous sickness history) + 2.4 (gender) + 0.78 (history of motion sickness) – 3.2 (gender × previous sickness history)

• Koivuranta– Score=0.93 (if female) + 0.82 (if previous PONV)

+ 0.75 (if duration of surgery over 60min) + 0.61 (if nonsmoker) + 0.59 (if history of motion sickness)

• Apfel et al– four predictors: female gender, history of motion

sickness or PONV, non-smoking status and the use of opioids for postoperative analgesia

– none, one, two, three or four of these risk factors present, the incidences of PONV: 10, 21, 39, 61 and 79 %

Review of Anesthetic Meds

Nalbuphine• Synthetic opioid used commercially as an

analgesic

• SIDE EFFECTS– CNS effects: Nervousness, depression, restlessness,

crying, euphoria, floating, hostility, unusual dreams, confusion, faintness, hallucinations, dysphoria, feeling of heaviness, numbness, tingling, unreality. The incidence of psychotomimetic effects, such as unreality, depersonalization, delusions, dysphoria and hallucinations

– Cardiovascular: Hypertension, hypotension, bradycardia, tachycardia, pulmonary edema.

– Gastrointestinal: Cramps, dyspepsia, bitter taste.– Respiration: Depression, dyspnea, asthma.– Dermatological: Itching, burning, urticaria.

Promethazine• first-generation H1 receptor

antagonist

• SIDE EFFECTS: – confusion in the elderly; drowsiness,

dizziness, fatigue, more rarely vertigo; dry mouth; respiratory depression; constipation; chest discomfort; euphoria (very rare, except with high IV doses and/or co-administration with opioids/CNS depressants); restless legs; paresthesia

Fentanyl• Opioid

– 100x more potent than morphine

• USE: Anaesthetic and analgesic

• SIDE EFFECTS– SERIOUS: weak, shallow breathing, severe

weakness, drowsiness, or confusion; cold, clammy skin; or feeling light-headed or fainting.

– LESS SERIOUS: nausea, vomiting, stomach pain, constipation; dizziness, drowsiness, headache; swelling; or pain or mouth sores where the tablet was placed.

Propofol• short-acting, intravenously

administered hypnotic agent

• SIDE EFFECTS:– Pain on injection– Low blood pressure– Transient apnea– (Rare) Dystonia

Atracurium• intermediate-duration,

nondepolarizing, skeletal muscle relaxant for intravenous administration

Ketorolac• NSAID– Inhibits COX-1 and COX-2 thereby

inhibiting PG production• USE: short term management of

severe to acute pain• SIDE EFFECTS: – rash, ringing in the ears, headaches,

dizziness, drowsiness, abdominal pain, nausea, diarrhea, constipation, heartburn, and fluid retention. stomach ulceration and intestinal bleeding renal impairment allergic reactions

Morphine • Phenanthrene opioid receptor

agonist – Interacts with μ-opioid receptor– Induces analegsia by mimicking

endogenous endorphin release

• principal effect on CNS and GI– Analgesia, sedation, euphoria

Morphine• SIDE EFFECTS• Bradycardia, Cardiac arrest,

Hypotension, Palpitation,syncope, Flushing of the face, Orthostatic hypotension, Pruritus or itching, Xerostomia or dry mouth, Intermittent blurring, miosis, Visual distortions, Constipation, Nausea and vomiting or emesis, Hepatotoxicity, Renal failure, Bradypnea, dyspnea or respiratory depression

Differentials for Post-op Nausea and Vomiting

Differentials• Anaesthetic-induced– Opioid: fentanyl and morphine

• Hypotension– Secondary to anaesthetic agent or

to blood loss during surgery– Highly unlikely

Opioid-inducedNausea and Vomiting

Opioids• highly effective analgesics• WHO's pain ladder – step-wise approach to the use of

analgesics– third and final step for severe pain. 

• Nausea and vomiting– undesirable side effects associated

with the use of the opioid analgesics

Etiology & Risk Factors• Medication with opioids is a major

contributory factor to post-operative nausea and vomiting. – For example the incidence of nausea and vomiting in

patients undergoing minor gynaecological surgery has been reported to increase from 18% in a control group to more than 60% in patients receiving morphine or pethidine

• Factors: type of opioid analgesic used, time course, route of administration; previous exposure to opioids

Cause• Opioids have direct action on

the CTZ thru the 3 receptors (kappa - κ, delta - δ and mu - μ)

Consequences• When opioids are used post-

operatively patients have little opportunity to develop tolerance to the emetic effects – compared to chronic opioid users

i.e. cancer patients 

Consequences

Practicalvery distressing for

patients when they are already

feeling uncomfortable and anxious

Medicalpowerful muscular contractions may damage stitches, risk of bleeding, regurgitation of

stomach contents, poss. aspiration pneumonia; e- imbalance and dehydration, if

severe

Economic personnel time in

clearing up, material costs of disposable products, laundry, caring for patients, delayed discharged,

unplanned admission leading to bed

blocking, delayed surgical throughput and potential re-op

costs

*Audit Commission Report: most common cause for unplanned overnight hospiltalization after surgery is PONV

Management• Anti-histamines• Anti-muscarinics• Dopamine receptor antagonists• Opioid receptor antagonists– But will inhibit desired analgesic

effect

Management

Novel Antiemetics• Neurokinin-1 antagonist– Indirectly works on substance P, member

of the tachykinin family of neuropeptides, an important neurotransmitter in afferent pathways of emesis

– Works on NK1 receptor, a G-protein coupled receptor in the CNS, important in tachykinin peptide activity

– potential NK1 receptor blocking activity located deeper in the brain stem is thought to prevent both acute and delayed emesis

Novel Antiemetics• Long Acting Serotonin

Antagonist– Longest elimination half-life (40

hours) of all the currently available serotonin antagonists Its long

– also has high binding affinity for 5-HT3 receptors

Recommendations: PONV prophylaxis• No prophylaxis for low risk

patients except if at risk for medical consequences from vomiting (e.g. wired jaw)

• Moderate to high risk : regional anesthesia

• High risk: combination antiemetics and multimodal therapy

Recommendations: treatment for established PONV• paucity of data on the use of

anti-emetics for the treatment of PONV in patients who failed prophylaxis or did not receive prophylaxis

Recommendations: treatment for established PONV• 5-HT3 receptor antagonists

were the most commonly tested drugs – small doses of these agents have

been recommended for treatment• ondansetron 1 mg• dolasetron 12.5 mg• granisetron 0.1 mg• tropisetron 0.5 mg

Recommendations: treatment for established PONV• Within 6 hours post-op:– a drug from a different class

should be used for rescue

• Beyond 6 hours– may use any of the agents used

for prophylaxis except dexamethasone and scopolamine, which are longer acting

History of PONV

Regional anesthesia•Adequate hydration•Avoid nitrous oxide•Avoid high dose neostigmine

Female gender•Postoperative opioid•History of motion sickness•Long duration of surgery•Emetogenic surgery•Non-smoker

- 5-HT3 antagonist + Dexamethasone- 5-HT3 antagonist + Droperidol*- 5-HT3 antagonist +Acupuncture

≥ 2 antiemeticsPLUSTIVA with Propofol

PONV reduction strategy

A or3 factors in B A or/and <3 factors in B

consider

Guidelines for management - Society of OBB-GYN in Canada• Basically has the same

recommendations

• Acupoint electrical stimulation may be used as an alternative or adjuvant therapy for prevention of PONV

Pharma

Single Agent

CombiTherapy

Non-Pharma

Accupuncture

Pharma

Single Agent

CombiTherapy

Non-Pharma

Accupuncture

Single Agent

Metoclopramide: Pharmacodynamics• Antagonist to dopamine D2 receptors

of the CTZ• Mixed 5-HT3 receptor antagonist/5-

HT4 receptor agonist.– Contribute to antiemetic effect at higher

doses– prokinetic action

Metoclopramide: Pharmacokinetics

• rapidly and well absorbed• absolute oral bioavailability of

metoclopramide is 80% ± 15.5• peak plasma concentrations occur at

about 1 to 2 hr after a single oral dose– similar time to peak is observed after

individual doses at steady state.

Metoclopramide: Pharmacokinetics

• area under the drug concentration-time curve increases linearly with doses from 20 to 100 mg.

• peak concentrations increase linearly with dose

• whole body clearance is unchanged;

• elimination half-life in individuals with normal renal function is 5 to 6 hr

Metoclopramide: Pharmacokinetics

• 85% eliminated in the urine,– about half is present as free or conjugated

metoclopramide.• not extensively bound to plasma proteins

(about 30%).• HIGH whole body volume of distribution is high

(about 3.5 L/kg)• Renal impairment affects the clearance of

metoclopramide.– kinetics of metoclopramide still linear– The reduction in clearance – Downward dose adjustment should be done

Pharma

Single Agent

CombiTherapy

Non-Pharma

AccupunctureCombi

Therapy

Combination Antiemetic Therapy• Based on the concept that least

four major receptor systems are involved in PONV

• First introduced in 1988• Most of these studies suggest:

two or more antiemetics acting on different receptors are better than monotherapy for prophylaxis

Combination Antiemetic Therapy• Use two or more• Acting at different receptors– 5-HT receptor antagonist +

droperidol or dexamethasone: better PONV porphylaxis than 5-HT receptor antagonist alone

– Habib AS, El-Moalem HE, Gan TJ. The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials. Canadian Journal of Anaesthesia 2004;51:311-9.

Combination Antiemetic Therapy• Apfel CC, Korttila K, Abdalla M et al. A factorial trial of six

interventions for the prevention of postoperative nausea and vomiting.[see comment]. New England Journal of Medicine 2004;350:2441-51.

• 3 antiemetic interventions– ondansetron 4 mg– droperidol 1.25 mg– dexamethasone 4 mg

• 3 anesthetic interventions – (TIVA with propofol, omitting nitrous oxide, and

substituting remifentanil for fentanyl) for the prophylaxis of PONV

Combination Antiemetic Therapy• Conclusion: – Antiemetics with different mechanisms

of action have additive rather than synergistic effects on the incidence of PONV

– Each antiemetic reduced risk by 25%– When combinations of interventions

were used, the benefit of each subsequent intervention was always less than that of the first intervention

– Efficacy depends on patient’s baseline risk

Multimodal Therapy• Since PONV is multifactorial etiology, a

multimodal therapy is also suggested• Study by Scuderi et al: multimodal

approach to the management of PONV in females undergoing outpatient laparoscopy– Multimodal management: 98% complete

response rate (no PONV and no antiemetic rescue) in PACU. No patient in this group vomited before discharge,

– Ondansetron group: 7 % of patients – Placebo group: 22 % of patients

Pharma

Single Agent

CombiTherapy

Non-Pharma

AccupunctureAccupuncture

Acupuncture and PONV • stimulation at the Pericardium

(P6) acupuncture point (acupoint) on the wrist will have a reduced risk of nausea and vomiting after surgery

• needle acupuncture, transcutaneous nerve stimulator, laser stimulation and acupressure wristbands

Acupuncture and PONV • 4,500 patients from 1986 to

2008 – 32 studies: P6 acupoint

stimulation vs placebo (3,385 patients)

– 14 studies: P6 acupoint stimulation vs antiemetic treatment (1,036 patients)

• compared to placebo, stimulation of the P6 acupoint reduced the risk of nausea and vomiting after surgery, with fewer side-effects

Summary

Summary• Many opioids are very effective

analgesics and they are frequently used for post-operative analgesia and in palliative care

• Nausea and vomiting are undesirable side effects associated with the use of opioids

• Medication with opioids is a major contributory factor to post-operative nausea and vomiting (PONV), though tolerance can develop when used chronically, for example in palliative care.

Summary• Opioids are thought to induce nausea

and vomiting by a direct action on the chemoreceptor trigger zone (CTZ).

• Opioid-induced nausea and vomiting can be distressing to patients, may have medical implications and has economic consequences

• Anti-histamines, anti-muscarinics and dopamine receptor antagonists have efficacy against opioid-induced nausea and vomiting.

Reference

Main Journal• Gan TJ, Meyer T, Apfel CC,

Chung F, Davis PJ, Eubanks S, et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003;97;62–71.