Presentation on theme: "Management of Acute Pain, Nausea, and Emesis"— Presentation transcript:
1Management of Acute Pain, Nausea, and Emesis Joseph Bubalo PharmD, BCPS, BCOPOncology Clinical Pharmacy SpecialistAssistant Professor of Medicine
2Acute Pain and Nausea Management Overview AssessmentTherapeutic optionsMonitoring/management
3Pain AssessmentHistory of past pain medication use as well as history of recreational or substance abuse activity, including alcohol.List of current medications (RX and OTC) and supplements (herbal, nutritional, homeopathic, etc)Allergy/sensitivity History
4Pain AssessmentLocation – find all locations and intensity at each. Get an overall pain score.Character – sharp, dull, aching, constant, intermittent, burning, etc.Frequency and pattern.Severity.Has it changed or what makes it better/worse?Known etiology?
5Pain AssessmentWhat have they tried (pharmacologic and non-pharmacologic) and what were the results?Therapy, dose, duration, how results were evaluated.What are the patient’s expectations/goals?Initial evaluation and follow-up must be done a bedsideFollow-up over time – is a change new pain as opposed to not enough drug?
11Analgesic Therapeutics Start at “normal dose”Base frequency on severity of pain, patient tolerance, pharmacokineticsIf chronic analgesics minimum of 25-30% of chronic dose for breakthrough to achieve efficacyTitrate to therapeutic dose and lengthen interval as analgesia occursConsider adjuvants and co-analgesics
12Duration of TherapyBased upon etiology …the expected duration of pain will varySomatic, abdominal, neuropathicFixed pain course?Acute pain – Subsides over an “expected” period of timeAcute exacerbation of chronic painReturn to baseline or titrate to new baseline
13Renal and Hepatically Impaired Patient Choose agent with fewest active metabolitesDose to effect than titrate slowly at increased intervalsAgents of choice - hydromorphone, oxycodone, and fentanylContraindicated agents – meperidine, propoxyphene
14The Opioid Naive Assess type and duration of pain Analgesic doses used thus far and response/side effectsPCA OK, but no basalFrequent reassessmentMost at risk: small, elderly, organ compromised
15Opioid Tolerant Chronic pain patient Recreational user Figure 24 hour usageBase rescue dosing at 10% of 24 hour use or 25-30% of incremental dose at the normal intervalAssess bowel function
16PCA GuideInitial basal may be used to replace chronic dosing otherwise leave off during initial assessment periodBreakthrough frequency generally 6, 10, or 15 minutesChoices – Morphine 1 mg = hydromorphone 0.2 mg = fentanyl 10 mcgGive range to allow titration for more effective dosingNaloxone part of protocol orders
17PCA Safety Issues PCA by proxy Patient education Monitoring For appropriate analgesiaTo prevent oversedationVideogame thumbMonitoringPain, alertness, vitals Q 4H-rate/quality of respirations first hours.Product selectionPt Ed – Be sure patient is capable of operating a PCA and knows they don’t have to keep pushing the button if they are comfortable. Products available are hydromorphone, MS, and fentanyl. Respirations, heart rate, and blood pressure the first hours important to monitor. Increased risk of nocturnal hypoxia the first 1-2 days.
18Adjuvants/Coanalgesics LaxativesNSAIDsAnti-anxietyAntiemeticsHypnoticsMuscle relaxantsLocal anestheticsConsider additive side effects and potential to exacerbate co-morbidities
19Opioid Side EffectsRespiratory depression – titration rate based on analgesic need, reduce dose if cause of pain relieved. Rare after 3-4 days.ConstipationItching – Antihistamines or change agent. True allergy rareNausea – Antiemetics, take with food, change agent or routeHallucinations – Change agent or routeSedation – Rule out other causes, change agent, add stimulantUrinary retention – Change agent or add bethanacol
20General Management of Nausea and Vomiting SickExpulsionHurlPukeRetchingSpewHonkRalphOwVomitoGagGeneral Management of Nausea and VomitingUpchuckHeaveSpit UpRegurgitationUpset StomachBlowChunksOh- mandarin, vomito- spanish, Ow - cantoneseBarfEmesisHyperemesisDisgorgementThrow upOH
21The First Emesis?feb 2002, Fossilized "dinosaur" vomit has been discovered in a quarry in Peterborough. Scientists believe the vomit, estimated to be 160 million years old, gives vital clues to the feeding habits of ichthyosaurs, marine reptiles that lived at the same time as the dinosaurs.Detailed analysis has revealed the remains of dozens of belemnites - an ancient sea creature - within the fossilized substance.Peter Doyle has studied the prehistoric vomit Professor Peter Doyle, of the University of Greenwich, believes the belemnite shells contained in the vomit indicate that they were regurgitated.The process is shared by the modern-day sperm whale.Professor Doyle said: "It is highly unlikely that these shells passed through the ichthyosaur's intestines and were excreted as droppings because they would have damaged the soft tissue of the reptile's internal organs."The only alternative is that the shells were vomited out in much the same way that modern-day sperm whales regurgitate the indigestible beaks of squid."Chronic indigestionFurther examination has revealed distinctive etching marks on the shells.These are believed to have been caused by the digestive fluids from the gut of the ichthyosaur.Ichthyosaurs swam in the ocean when dinosaurs walked on land.They appeared slightly earlier than dinosaurs (250 million years ago) and lived until about 90 million years ago.Professor Doyle said: "The Peterborough belemnite shells have revealed acid etching marks, proving that they had been eaten by a predator."The fact that most of these belemnites were juveniles reinforces our view that they did not die of old age."The research team believes the acid etching marks provide the first hard evidence that ichythosaurs vomited the inedible parts of shellfish to avoid internal damage and chronic indigestion.
22Assessment of N/V GI status – Obstructed or not Frequency – nausea/emesisVolume – emesis and contentsTiming – Proximate cause, worse in AM/PM?Hydration status?
25Cerebrum Motion/spaceH1, M, 5HT1a Emetic center 5HT3, D2, M, NK1 Sensory input (pain, smell, sight)CerebrumMemory, fear, dreadMotion/spaceH1, M, 5HT1aInner earEmetic centerNucleus tractus solitarious (NTS)5HT3, D2, M, H1, NK1Chemoreceptor Trigger Zone (area postrema)5HT3, D2, M, NK1CNSPeripheryVagal and sympathetic afferentsPharynxBlood brain BarrierGI tract5HT3, SPBlood born toxinsLocal irritantsCalcium causes an exocytic release of serotonin from enterochromaffin cells in the GI tract, possibly as a result of free radical generation. The release serotonin activates vagal afferent receptors which stimulate the CNS. 5HT3 receptors are also in the area postrema, NTS, subnucleus gelatinosus, the lower densities of the vagus. Substance P is co-localized with serotonin in the enterochromaffin cells of the GI tract.
27Therapy/Drug Selection Issues Drug affinity for probable cause (receptors, pharmacodynamics, etc)Available routes of administrationSide effect profilePatient ContraindicationsTreat underlying condition if possible
28Major “Antiemetic” Drug Classes Serotonin (5-HT3) receptor antagonistsDopamine (D2) receptor antagonistsNeurokinin 1 antagonists (NK1a)Substituted benzamides (metoclopramide)SteroidsBenzodiazepines (BZ)CannabinoidsHistamine (H1) receptor antagonistsMuscarinic receptor antagonistsThe 5-HT3 receptor antagonists have been available in the US since 1991 and represent the largest therapeutic advance in the control of chemotherapy-induced emesis.Lorazepam, a benzodiazepine, is used to control anxiety, induce amnesia, and decrease the stress of receiving chemotherapy; antiemetic activity has been suggested for this drug.*Cannabinoids are used in the treatment of CIE; however, their use is limited by the many CNS side effects caused by these agents including sedation, mood changes, memory loss, euphoria, and hallucinationsDopamine receptor antagonists (including the phenothiazines, the butyrophenones, and domperidone) may produce extrapyramidal side effects, they have been used to prevent CIE, radiotherapy-induced emesis, and postoperative nausea and vomiting (PONV).Histamine H1 receptor antagonists are used to treat postoperative vomiting and motion sickness.Muscarinic receptor antagonists include scopolamine (hycosine) and atropine, both of which are used to control PONV and motion sickness.Pyridoxine (vitamin B6) has been used to treat pregnancy-associated nausea and vomiting and radiotherapy-induced emesis, but its efficacy has never been clearly established.Steroids, such as dexamethasone and methylprednisolone, are used to control CIE; their antiemetic mechanism of action is unknown, but it may be mediated through inhibition of prostaglandin synthesisSubstituted benzamides, such as metoclopramide, are used to treat CIE; at high does, they may produce extrapyramidal side effects.*This indication is not approved by the FDA for use in the United States.
29Agents and IssuesMetoclopramide – GI stasis or lower sedation level neededDexamethasone – inflammatory component, cerebral edema, additive effect neededOctreotide - Bowel obstruction in terminal disease or those who fail anticholinergicsBenzodiazepines – anxiety, phobias, learned behaviors
30Agents and IssuesPhenothiazines – Broadly active, especially in combinationHaloperidol, droperidol – similar to phenothiazines in spectrum of activityMeclizine, dimenhydrinate, scopolamine – vestibular componentHyoscyamine – for nausea secondary to excess bronchial or gastric secretionsSerotonin antagonists – Drug of last resort
31Agents and DosesMetoclopramide mg IM/IV/PO Q 4H PRN ( mg/day on average)Droperidol mg IV/IM Q 4H PRNHaloperidol mg Q 6 H PRNProchlorperazine mg IV/IM/PO Q 4H PRN*Promethazine mg IV/IM/PO/PR Q 4H PRNChlorpromazine mg IV/PO Q 4H PRN* Also have PR Option
32Additional Agents Dexamethasone 4-8 mg IV/PO QD to QID Scopolamine patch 1.5 mg (up to 8 hours for effect)Dimenhydrinate mg IV or mg PO Q 4H PRNMeclizine mg q 8 H PRNTrimethobenzamide 200 mg IM/PR Q 6H PRN
33Serotonin(5HT3) Antagonists for General N/V Ondansetron4 mg IV or 8 mg POGranisetronmg IV/PODolasetronmg IV or 50 mg POAll dosed one to two times daily
34Additional Routes Sub Q Metoclopramide, octreotide, haloperidol, dexamethasone, scopolamineDon’t give Sub-Q (cause irritation and erosions)Chlorpromazine, diazepam, prochlorperazine, promethazine, hydroxyzineSublingualLorazepam, hyoscyamine, haloperidol
35Is Droperidol Evil?03/01 UK’s Medicine Control Agency reviews QT issues and Janssen Dc’s Droleptan® and injectable droperidol after risk benefit assessmentFDA reviews drug and receives 273 reports for 11/97-12/01 with many being duplicatesMajority of events occurred at doses > 10 mg10 deaths, 18 cardiac arrests, 6 cases of QTc prolongation and 3 of torsades de pointes reported at doses < 2.5mg in 30 years10 Serious case reports at doses < 1.25 mg, none of which showed a causal relationshipHorowitz BZ, et al Academy of Emergency Medicine 2002;9(6);615-8
36Droperidol Effects Normal QTc is 440 msec males and 450 msec females Prolonging QTc more than 500 msec or 60 msec increases the risk for dysrhythmiaQT prolongation fatal arrhythmia/ cardiac arrest0.1, 0.175, and 0.25 mg/kg doses equivalent in a 70 kg adult to 7, 12.25, and 17.5 mg caused a 37, 44, and 59 msec QTc prolongation respectively.Before 2001 warning for doses > 25 mg causing sudden death if at risk for cardiac dysrythmiasLischke V, et al Anesthesia and Analgesia 1994;79:983-6
37Droperidol May be evil … However Droperidol is associated with QTc prolongationThis temporal and dose dependent association has not been proven to be related to torsades de pointes in any type of randomized or controlled settingCase reports suggest that rare cardiac events may be associated with droperidol administration but none are causally associated with it’s useAnalogous situations exist with other medications including haloperidol, cyclobenzaprine, and 5HT3 antagonists
38Droperidol Recommendations Ongoing safety monitoring should occurAvoid use with other agents which prolong the QT interval, change target drug metabolism, or in patients with known cardiac dysrhythmiasConsider ECG monitoring if elevated doses are required or use is indicated in a patient with known risk factorsUse the minimum effective doseConsider alternative agents if doses > 5mg are indicatedKao LW et al Annals of Emergency Medicine 2003;41:546-58
39Combinations D2 Antagonist 5HT3 Antagonist Other Metoclopramide ProchlorperazineHaloperidolDroperidolPromethazine5HT3 AntagonistOndansetronOtherDexamethasoneLorazepamDronabinolDimenhydrinateDiphenhydramineMeclizineScopolamineHyoscyamineTrimethobenzamide
40NonPharmacologic Approaches Decrease Milk productsClear liquid dietBland dietDecrease sources of smell (cold and room temperature food)Manage anxietyDistraction techniques, guided imageryNG tube
41Other Issues Multiple agents common Ginger, Peppermint oil Hydration AcupressureMarijuana