Immunity and Sepsis Flashcards
Zidovudine + corticosteroids
severe myopathy
respiratory muscle dysfunction
Nucleoside reverse transcriptase inhibitors
considerations
- inhibition cytochrome P450 (zidovudine + corticosteroids can = severe myopathy including respiratory muscle dysfunction)
- Lactic acidosis is a huge issue – may have a lower threshold for getting a blood gas
- Nausea, diarrhea, myalgia,
- ↑ LFTS, pancreatitis,
- peripheral neuropathy (possible nerve injury),
- renal toxicity,
- marrow suppression,
- anemia
HIV drug that decreases fentanyl clearance
Protease inhibitors (ritonavir)
inhibition of CYP450 3A4
(↓ fentanyl clearance ~ 67%)
titrated fentany more conservatively
Protease inhibitors (ritonavir)
considerations
- Hyperlipidemia
- glucose intolerance → higher blood glucose levels
- abnormal fat distribution
- altered LFTs
- inhibition of CYP450 3A4
Non-nucleoside analog reverse transcriptase inhibitors
considerations
- Delavirdine inhibits cytochrome P450
- may ↑ concentrations
- sedatives
- antiarrhythmics
- warfarin
- Ca2+ channel blockers
- may ↑ concentrations
- Nevirapine induces cytochrome P450 by 98%!
- Make sure you are checking things like NMB
Integrase strand transfer inhibitors
considerations
appear well tolerated
Chemokine receptor 5 antagonists & entry inhibitors
considerations
interact with midazolam altering clearance & drug effect
HAART therapy and anesthesia
institution of HAART within 6 months of anesthesia & surgery actually ↑ M&M
Ritonavir (Protease inhibitor) & Interactions with Anesthetic Drugs
- Midazolam: ↑ effects
- sedation, confusion, respiratory depression
- Small carefully titrated IV dosing O.K. (just do it very slowly and carefully- working in very tiny incraments one consents are sighned)
- Fentanyl: ↑ effects
- sedation, confusion, respiratory depression
- Start with low dose & titrate to pain
-
Avoid (pronounced effects → life threateningàdue to prolonged clearance)
- Meperidine → metabolized to normeperidine → which affects CNS (seizures) even with one dose may end up with a toxic dose
- Amiodarone (arrhythmias) → E½ life = 29 days - may not always think about this with ACLS but is something to keep in the back of your mind
- Diazepam → long ½ life
sterilization product that destroys HIV
Na+ hypochlorite
HIV and Lab results
- CD4 counts
- low/ominous
- high/encouraging >500-700 mm3
- if low, maybe want them to go and change drug regimen prior to surgery
- T lymphocyte counts
- low/ominous 200 cells/mg
- Viral load evaluates therapy efficacy but unclear significance to anesthetic outcome – wont tell us how they will do under anesthesia, drugs will still effect all other systems of these patients
- CBC
- BMP
- coagulation studies
- CXR
- EKG+/- ECHO
- PFTs
TB drugs that are hepatotoxic
isonazid
Rifampin
Pyrazinamide
TB drugs that are hepatotoxic AND renal toxic and have significant drug interactions
Isoniazid
Rifampin
** these are also the most used**
Isoniazid adverse rxn
Hepatotoxicity
peripheral neurotoxicity
possible renal toxicity
drug interactions
Rifampin adverse rxn
Hepatotoxicity
renal toxicity
anemia
thrombocytopenia
gastrointestinal upset
drug interactions
Pyrazinamide adverse rxn
Hepatotoxicity
gastrointestinal upset
arthralgia
Ethambutol adverse rxn
Ocular neuritis
when can a TB patient have an elective surgery
- 3 negative sputum smears
- improving symptoms
- clear chest X-ray
! must meet ALL 3 requirements to go to surgery !
when do you give antibiotics?
- normal pt: within 1 hr before surgery
- redose if surgery > 4 hrs
besides antibiotics how else do you prevent infections
AVOID:
-
Hypothermia
- Cold pts develop infections at a much higher rate!
- They also bleed more!!!
-
Hypocarbia
- promotes infection causes vasoconstriction which decreases blood flow
- make sure you are not hyperventilating the patient
- Hypoxia
-
hyperoxia
- concerning for free radical damage
- Hyperglycemia
-
Blood transfusions
- if you can avoid it is its ideal – they are at higher risk to get an infection
Endocarditis prophilaxis - who gets it?
Patients who have:
- Artificial heart valves
- Prior history of endocarditis
- Some congenital cardiac malformations
- Cyanotic congenital heart disease (birth defects with O2 levels lower than normal), that has not been fully repaired, including children who have had a surgical shunts & conduits, or those with prosthetic device with a repaired
- A congenital heart defect that’s been completely repaired with artificial material or a device for the first six months after the repair procedure
- Repaired congenital heart disease with residual defects, such as persisting leaks or abnormal flow at or adjacent to a prosthetic patch or prosthetic device
- Damaged heart valves
- Hypertrophic cardiomyopathy
- A cardiac transplant which develops a problem in a heart valve
AND undergoing the following surgeries:
- Dental or oral with perforation of the oral mucosa likely (dental extractions)
- Invasive procedures of respiratory tract where respiratory mucosa perforated
- I.e. Tonsillectomy, adenoids, abscess drainage
- Procedure involving infection of GI/GU tract, skin/musculoskeletal tissue (not needed with routine procedures; colonoscopy, upper endoscopy, cystoscopy (removal of renal stones) or even bronchoscopy)
- Cardiac Surgery
- Hepatobiliary procedures with high risk of bacteremia
When and what do you give for endocarditis prophylaxis
give up to 2 hours after if patient misses pre-procedure
- Ampicillin 2 g IV (50 mg/kg pediatrics)
- Cefazolin (Ancef) 1 g IV (50 mg/kg pediatrics)
- Ceftriaxone (Rocephin) 1 g IV (50 mg/kg pediatrics)
If allergic to penicillins
- Clindamycin 600 mg IV (20 mg/kg IV pediatrics)
Type I allergic rxn
Antigen-Antibody
- IgE, mast cells, basophils degranulation → anaphylaxis
- immune-mediated hypersensitivity
Type II allergic rxn
Cytotoxic-Complement Activation
- IgG or IgM binding of the antigen-drug
- alternate pathway, kinin or plasmin activation
- Type II usually manifest as hemolytic anemia, thrombocytopenia, neutropenia
Type III allergic rxn
Damage secondary to immune complex formation or deposition
Glomerulonephritis, vasculitis, arthralgias
Type IV allergic rxn
T lymphocyte mediated
delayed hypersensitivity type
Chemical Mediator allergic rxn
Chemical Mediator with no antigen-antibody reaction
mast cells & basophils activate in a non-immune reaction → anaphylactoid
I.e. MR, meperidine, morphine, etc.
Anaphylactoid Reaction
manifests as histamine release
related to total dose of drug administered & rate of infusion
(ex: muscle relaxants, opioids, & protamine)
Anaphylactoid Reaction prophylaxis
- Corticosteroid
- H1 & H2 receptor antagonist
I.e. decadron, benadryl, ranitidine
Anaphylaxis
- IgE mediated response
-
life threatening
- Extravasation of up to 50% of intravascular fluid volume into the EC space possible
- hypotension 1stsign
- bronchospasm - seen as increased PIP
- edema and airway swelling are late signs
Anaphylaxis: Common Offenders
-
Antimicrobial agents
- PCN → 90% of all allergic reactions & 97% of fatal reactions
-
Anesthetics
- All anesthetic agents can cause anaphylactic reactions with the exception of ketamine & benzos
- Thiopental has a low risk, but a very high mortality if they have an anaphylactic reaction
- Radiocontrast dyes
-
Foods
- I.e. peanuts
-
Insect venoms
- Bee allergy
Anaphylaxis: Anesthetic agents
-
Muscle relaxants
- 50-60% of intra-op anaphylaxis occurances
- actually much more likely to be casing than an antibiotic
-
protamine
- seafood & salmon allergy
- NPH insulin
-
Induction agents
- Consider ketamine to prevent reaction in high risk patients
- Antibiotics (10-15%)
- Volatile anesthetics
-
Opioids
- D/t histamine release
-
Local Anesthetics
- esters more likely than amides
-
Blood → even with crossmatch
- 3% of patients
- Dextran/Hetastarch
-
Vascular grafts
- DIC more than anaphylaxis
-
Latex
- 15% periop
Anaphylaxis: Differential Diagnosis
- Pulmonary embolism
- Pneumothorax – high peak inspiratory pressure
- AMI
- CVA
- Hemorrhage
- Aspiration
- Pulmonary edema
- Venous Air embolism
- Vasovagal reaction
- Medication overdose
- Asthma → shouldn’t produce immediate cardiovascular collapse
- Arrhythmia → one of the first signs from the muscle reactants these patients could become very bradycardic → may have a loss of profusion to the coronaries and look like an MI
- Pericardial tamponade
- Postextubation stridor
- Sepsis
Anaphylaxis: Signs & Symptoms
- Rapid onset CV collapse often 1st sign → myocardial ischemia & dysrhythmias
-
Hypotension → up to 50% of the ICF moves to ECF secondary to capillary permeability changes + leukotrienes are negative inotropes)
- this happens within minutes
- Suspect anaphylaxis with sudden hypotension, +/- bronchospasm, following IV drug administration
- Bradycardia may occur especially with muscle relaxants
- Difficult intubation → laryngeal edema (usually this is if it is in the later phase – keep in mind if they have an LMA or are masking you will need to intubate immediately because it will get worse and worse)
- ↑ PIP or inability to ventilate → bronchospasm
- Flushing, urticaria
Ketamine → propofol → epi
All could work in severe situation
anaphylaxis
most common offending abx
- β-lactam
- quinolones
- sulfonamides
- vancomycin
Anaphylaxis: Prompt Intervention
-
Communication (let everyone know → surgeon, additional personnel)
- should stop the case immediately until stable again
- Stop administration of likely agent(s)
- Oxygenation
- Elevate legs if possible to promote blood flow to central circulation
- Volume infusion → need at least 10-25 ml/kg
- Colloids fluids (10 ml/kg) are preferred to crystalloid fluids (colloids may stay in the intravascular space more)
- Fluids boluses over 20 minutes
Anaphylaxis: Pharmacology
-
Epinephrine – (always always start with epi but sometimes it does fail)
- Blocks inflammatory mediator release from sensitized cells
- Restores cell membrane permeability
- β-agonist effect = relaxation of bronchial smooth muscle, ↑ BP & ↑ inotropy
- β2 → bronchodilation, ↓ histamine release from mast cells; also best to revers bronchospasm
- β1 → will help heart compensate
- α1 stimulation → vasoconstriction & restore vascular integrity
- Adult IV: 10 mcg-1 mg titrate q 1-2 minutes
- Start with 10 mcg then double with each repeated dose
- Children: 1-10 mcg/kg titrate q 1-2 minutes
Anaphylaxis: if resistant to epinephrine
-
Glucagon: 1-5 mg bolus + infusion 1-2.5 mg/hr
- ↑ cAMP promotes inotropic activity and helps with the bronchoconstriction
-
Norepinephrine: 0.05-0.1 mcg/kg/min
- will not help the bronchospasm situation – but will help in shunting blood to central areas –emergency drug
-
Vasopressin: 2-10 unit bolus + infusion 0.01-0.1 unit/min infusion
- moves blood to central circulation
Anaphylaxis: secondary Pharmacology
Not necessarily life saving but will help slow down or stop reaction causing anaphylaxis
-
β2 agonists
- albuterol if patient is still moving air
-
Histamine antagonism
- Diphenhydramine (IV)(0.5-1 mg/kg IV) with Ranitidine 50 mg IV → better for prevention than for tx.
- H1 & H2 need to be blocked together - has the best effect
-
Corticosteroids:
- Enhances β-effects of other agents
- Inhibits arachidonic acid release (↓ leukotrienes & prostaglandins)
- Reduced activation of the complement system
-
Hydrocortisone is favored 250 mg IV
- (Methylprednisolone also OK 80 mg IV)
- Children:
- hydrocortisone 50-100 mg &
- methylprednisolone 2 mg/kg
- Get them on board as soon as possible - wont see immediate effects
Septic Patient - Anesthesia Optimization Goals
Delay case if not an absolute emergency
- Normal temperature
- Normal blood glucose
- MAP >65 mmHg
- CVP 8-12 mmHg
- Urine output adequate
-
Normalized pH
- correct metabolic acidosis - Plasmalite or Normasol- better compared to LR and NS because they are right at physiologic pH – it is maintained MUCH easier
- Mixed venous O2 Sat >70%
- Lower VT 6-8 ml/kg → to prevent barotrauma
- PIP
- Hgb 7-9 g/dL
- Prevent additional infection
Septic pt and epiduals
Don’t even try
Absolute contraindication to do an epidural anesthesia
- Especially with hemodynamic instability → patient may not tolerate ↓ SVR
- Epidural abscess if bacteremic blood introduced into epidural space
