11.3 Bronchodilators, Diuretics, Antacids, Corticosteroids & Uterotonics

11.3 Bronchodilators, Diuretics, Antacids, Corticosteroids & Uterotonics

Beyond anesthetics and cardiovascular vasoactive infusions, perioperative care demands mastery of diverse adjunctive drug classes. Anesthesia technologists routinely manage specialized delivery equipment for bronchodilators, inspect and filter osmotic diuretics, prepare aspiration prophylaxis regimens, reconstitute stress-dose steroids, and handle high-alert uterotonic agents. Understanding the pharmacology, specific delivery mechanics, and absolute contraindications of these specialty agents is vital for intraoperative vigilance and exam readiness.

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Perioperative Bronchodilators: Beta-2 Agonists & Anticholinergics

Acute intraoperative bronchospasm under general anesthesia presents with rising peak inspiratory pressures (PIP) alongside normal plateau pressures (Pplat), an upsloping expiratory capnogram waveform ("shark-fin"), diminished breath sounds, and wheezing. Rapid pharmacologic reversal requires targeted inhaled therapy.

Albuterol (Proventil, Ventolin)

• Mechanism of Action: Highly selective beta-2 adrenergic receptor agonist. Binding to beta-2 receptors on bronchial smooth muscle couples with the stimulatory G-protein (Gs), activating adenylyl cyclase. This converts intracellular ATP into cyclic adenosine monophosphate (cAMP). Elevated cAMP activates Protein Kinase A (PKA), which phosphorylates regulatory proteins, decreases intracellular free calcium, and deactivates myosin light-chain kinase. The resulting relaxation of bronchial smooth muscle produces rapid bronchodilation within minutes.
• Delivery in Mechanically Ventilated Patients: Standard handheld inhaler spacers cannot be interfaced directly with a closed breathing circuit. The anesthesia technologist must install a dedicated in-line Metered Dose Inhaler (MDI) adapter (such as an elbow or T-piece adapter) into the inspiratory limb of the breathing circuit close to the patient wye.
  • Administration Protocol: Deliver 4 to 8 puffs, actuating the canister synchronously at the very initiation of the mechanical inspiratory cycle, followed by a 2- to 3-second inspiratory pause to maximize distal aerosol deposition in terminal airways. Alternatively, continuous in-line pneumatic or vibrating-mesh ultrasonic nebulizers are placed in the inspiratory circuit limb.
• Adverse Effects:
  1. Sinus Tachycardia: Cross-reactivity with cardiac beta-1 receptors at higher doses, combined with reflex tachycardia secondary to peripheral beta-2 vasodilation.
  2. Skeletal Muscle Tremor: Stimulation of beta-2 receptors on skeletal muscle fibers.
  3. Hypokalemia: Beta-2 stimulation directly activates the Na+/K+ ATPase pump on cell membranes, driving potassium from the extracellular space into skeletal muscle and hepatic cells. (This mechanism is frequently utilized intentionally to treat life-threatening acute hyperkalemia).

Ipratropium Bromide (Atrovent)

• Mechanism of Action: Synthetic quaternary ammonium derivative of atropine. Acts as a competitive antagonist at muscarinic M3 receptors located on bronchial smooth muscle and submucosal mucus glands. By blocking postganglionic parasympathetic cholinergic tone mediated by the vagus nerve, ipratropium inhibits acetylcholine-induced bronchoconstriction and dramatically decreases bronchial secretions.
• Clinical Utility & Synergy: Slower onset (15 to 30 minutes) than albuterol, but provides an additive, synergistic bronchodilator effect when combined with beta-2 agonists (Combivent / DuoNeb), particularly in patients with chronic obstructive pulmonary disease (COPD).
• Pharmacokinetic Advantage: Because of its permanent quaternary ammonium charge, ipratropium is poorly absorbed across mucosal membranes and cannot cross the blood-brain barrier. Consequently, systemic anticholinergic side effects (tachycardia, central anticholinergic syndrome, pupillary dilation, urinary retention) are negligible compared to intravenous atropine or glycopyrrolate.

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Perioperative Diuretics: Loop & Osmotic Agents

Diuretics are administered perioperatively to treat acute volume overload, reduce elevated intracranial or intraocular pressure, and induce forced diuresis.

Furosemide (Lasix)

• Mechanism of Action: High-ceiling loop diuretic. Reversibly binds and inhibits the luminal Na+-K+-2Cl- cotransporter (NKCC2) in the thick ascending limb of the loop of Henle:

LUMEN (Urine): [Na+] [K+] [2 Cl-] ===X===> [NKCC2 Transporter Inhibited by Furosemide]
                                                |
                                                v
                               Abolishes Medullary Hypertonicity
                               Water Cannot Be Reabsorbed in Collecting Duct
                               Profound Excretion of Na+, K+, Cl-, Mg2+, Ca2+, H2O

• Physiological Impact: By blocking ion reabsorption in the thick ascending limb, furosemide eliminates the hypertonic medullary osmotic gradient. Solutes and free water remain trapped in the tubular lumen, producing rapid, heavy diuresis.
• Dosing & Onset: 10 to 40 mg IV bolus (titrated up to 100-200 mg in chronic renal insufficiency). Onset is within 5 minutes, peaking at 30 minutes, with a duration of 2 hours.
• Clinical Indications: Acute pulmonary edema, congestive heart failure, fluid overload from massive fluid resuscitation, and acute oliguria.
• Complications: Hypokalemia, hypomagnesemia, hypochloremic metabolic alkalosis, intravascular volume depletion (hypotension), and ototoxicity (manifesting as tinnitus or transient/permanent sensorineural hearing loss if administered as a rapid IV bolus exceeding 4 mg/min).

Mannitol: Osmotic Diuresis & Technical Handling

• Pharmacology: A non-reabsorbable six-carbon sugar alcohol (hexitol, molecular weight 182.2 Da). Mannitol is freely filtered at the glomerulus but undergoes negligible tubular reabsorption, elevating the osmolality of tubular fluid and inhibiting water reabsorption in the proximal tubule and descending limb of Henle.
• Neurosurgical Mechanism: Mannitol cannot penetrate an intact blood-brain barrier (reflection coefficient sigma = 0.9). Infusion creates an osmotic pressure gradient between circulating plasma and brain tissue, drawing free water from brain intracellular and interstitial compartments into the cerebral microvasculature. This acutely shrinks normal brain parenchyma, lowering Intracranial Pressure (ICP) and decreasing brain bulk to facilitate surgical exposure during craniotomy.
• Dosing: 0.25 to 1.0 g/kg IV administered as an infusion over 15 to 30 minutes.
• Biphasic Hemodynamic Consequences:
  • Initial Phase (Transient Hypervolemia): Within the first 5 to 15 minutes, the rapid transcellular extraction of water expands intravascular volume. In patients with poor left ventricular reserve or congestive heart failure, this sudden volume expansion can precipitate acute pulmonary edema.
  • Secondary Phase (Profound Diuresis): Intense osmotic diuresis follows within 15 to 30 minutes, leading to hypovolemia, arterial hypotension, and hypernatremic dehydration.
• Physicochemical Handling & Mandatory Filtration: Mannitol is formulated as a concentrated, supersaturated aqueous solution (commonly 20% = 200 mg/mL). At cool room temperatures or during storage, mannitol readily crystallizes into visible needle-like precipitates.
  • Inspection Protocol: Anesthesia technologists must visually inspect every vial or IV bag of mannitol against light before dispensing. If crystals are detected, the container must be warmed in a fluid warming cabinet or warm water bath and agitated until completely dissolved, then cooled to body temperature before infusion.
  • Mandatory Filter: Mannitol MUST ALWAYS BE INFUSED THROUGH AN IN-LINE INTRAVENOUS PARTICULATE FILTER (typically a 5-micron filter). This prevents microscopic, undissolved mannitol crystals from entering the patient's bloodstream and causing pulmonary microvascular occlusion or renal tubular obstruction.

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Gastrointestinal Pharmacology & Aspiration Prophylaxis

Pulmonary aspiration of gastric contents is a devastating anesthetic complication. Mendelson's Syndrome (acute chemical aspiration pneumonitis) occurs when aspirated gastric liquid has a pH < 2.5 and a volume > 0.4 mL/kg (approximately 25 mL in an adult). Acid liquid causes immediate chemical de-epithelialization of alveolar-capillary membranes, acute non-cardiogenic pulmonary edema, severe bronchospasm, and refractory hypoxemia.

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|                   PERIOPERATIVE ASPIRATION PROPHYLAXIS AGENTS                    |
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| 1. SODIUM CITRATE / CITRIC ACID (Bicitra)                                       |
|    - Class: Clear Oral NON-PARTICULATE Antacid.                                 |
|    - Dose: 30 mL orally administered 15 to 30 minutes prior to induction.      |
|    - Mechanism: Weak base that immediately buffers existing gastric HCl, raising|
|      gastric pH > 2.5 within 2 to 5 minutes.                                    |
|    - CRITICAL DISTINCTION: Non-particulate solutions cause minimal pulmonary     |
|      damage if aspirated. Particulate antacids (aluminum hydroxide, magnesium   |
|      trisilicate, calcium carbonate) can cause severe foreign-body pneumonitis  |
|      if aspirated.                                                              |
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| 2. FAMOTIDINE (Pepcid)                                                          |
|    - Class: Histamine-2 (H2) Receptor Antagonist.                               |
|    - Dose: 20 mg IV.                                                            |
|    - Mechanism: Competitively blocks H2 receptors on gastric parietal cells,    |
|      suppressing basal and stimulated gastric acid secretion.                   |
|    - Limitation: Requires 45 to 60 minutes for onset; does NOT buffer pre-      |
|      existing acid already present in the stomach lumen.                        |
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| 3. METOCLOPRAMIDE (Reglan)                                                      |
|    - Class: Dopamine D2 Antagonist & 5-HT4 Agonist Prokinetic.                  |
|    - Dose: 10 mg IV administered slowly over 1 to 2 minutes.                    |
|    - Mechanism: Increases lower esophageal sphincter (LES) tone, accelerates    |
|      gastric emptying, and relaxes the pyloric sphincter.                       |
|    - ABSOLUTE CONTRAINDICATION: Mechanical bowel obstruction, GI perforation,  |
|      pheochromocytoma, and Parkinson's disease (blocks central dopamine         |
|      receptors, triggering acute dystonic / extrapyramidal reactions).          |
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Why Non-Particulate Antacids Are Mandatory

The choice of antacid in anesthesia is strictly dictated by pulmonary pathology. Over-the-counter particulate suspensions (e.g., Maalox, Mylanta, Milk of Magnesia) contain insoluble mineral salts of aluminum, magnesium, or calcium. If a patient aspirates a particulate antacid during induction, the insoluble particles lodge in the small airways and alveoli and provoke a severe inflammatory, foreign-body pneumonitis that can be as damaging as acid aspiration itself.

In contrast, clear sodium citrate (Bicitra) is a non-particulate aqueous liquid that distributes evenly throughout gastric contents and causes minimal inflammatory reaction should microaspiration occur. Sodium citrate is the standard of care for emergency surgical cases, trauma patients with full stomachs, and obstetric patients undergoing emergent cesarean section.

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Perioperative Corticosteroids: Antiemetic & Stress-Dose Protocols

Dexamethasone (Decadron)

• Properties: Highly potent, long-acting synthetic glucocorticoid with an anti-inflammatory potency 25 to 30 times greater than cortisol, completely devoid of mineralocorticoid (sodium-retaining) activity.
• Postoperative Nausea & Vomiting (PONV) Prophylaxis: Dosed at 4 to 8 mg IV, administered immediately following the induction of anesthesia. Mechanisms include central inhibition of prostaglandin synthesis, suppression of cortical serotonin (5-HT) release, and reduction of systemic inflammatory cascades. Dexamethasone reduces the baseline risk of PONV by 25% to 30%, demonstrating powerful synergy when combined with 5-HT3 antagonists (e.g., ondansetron).
• Airway Edema Prophylaxis: Administered (4 to 8 mg IV) to prevent or reduce post-extubation laryngeal edema, stridor, and re-intubation in patients with traumatic intubation, airway surgery, prolonged prone positioning, or a negative cuff leak test (failure to hear air leak around a deflated endotracheal tube cuff).
• Adverse Effects: Mild transient elevation in blood glucose (monitoring required in diabetics). Rapid intravenous push injection produces intense, transient perineal burning, itching, or paresthesias ("perineal fire") lasting 30 to 60 seconds due to the phosphate ester carrier; this is prevented by diluting the dose in 10 mL saline and injecting slowly over 1 to 2 minutes.

Hydrocortisone (Solu-Cortef) & Stress-Dose Coverage

• Properties: Short-acting glucocorticoid with balanced mineralocorticoid activity (1:1 glucocorticoid-to-mineralocorticoid ratio, identical to endogenous cortisol).
• Pathophysiology of Adrenal Suppression: Under normal conditions, basal cortisol output is 15 to 20 mg/day, but surges to 100 to 300 mg/day in response to the surgical stress response. Patients receiving long-term glucocorticoid therapy (for example, prednisone 20 mg/day or more for longer than about 3 weeks) may develop hypothalamic-pituitary-adrenal (HPA) axis suppression; doses below 5 mg/day rarely cause it, and intermediate doses are uncertain. Under surgical trauma, these patients cannot mount an endogenous cortisol surge, resulting in acute perioperative adrenal crisis:
  • Manifests as refractory vasoplegic shock, severe arterial hypotension unresponsive to phenylephrine or norepinephrine, hypoglycemia, hyponatremia, and hyperkalemia.
• Perioperative Stress-Dose Coverage Regimens (examples; regimens vary by guideline and institution):
  • Minor Surgical Stress (e.g., hernia repair, diagnostic laparoscopy): 25 to 50 mg IV hydrocortisone on induction.
  • Moderate Surgical Stress (e.g., total joint arthroplasty, open cholecystectomy): 50 mg IV hydrocortisone on induction, then 25 mg IV every 8 hours for 24 hours.
  • Major Surgical Stress (e.g., cardiac bypass, esophagectomy, major vascular surgery): 100 mg IV hydrocortisone before induction, followed by 100 mg IV every 8 hours (or continuous infusion of 200-300 mg/day), tapering rapidly over 48 to 72 hours postoperatively.

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Uterotonic Pharmacology: Oxytocin, Methergine & Hemabate

Postpartum hemorrhage (PPH)—defined by ACOG as cumulative blood loss of 1,000 mL or more, or blood loss accompanied by signs or symptoms of hypovolemia, within 24 hours of birth—is a leading cause of maternal mortality. Uterine atony (failure of the myometrium to contract and compress intramyometrial spiral arteries) accounts for 70% to 80% of PPH cases. The anesthesia team directs pharmacologic uterotonic resuscitation.

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|                                 UTEROTONIC PHARMACOLOGY                                 |
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| 1. OXYTOCIN (Pitocin) - FIRST-LINE AGENT                                                |
|    - Class: Synthetic nonapeptide pituitary hormone.                                    |
|    - Mechanism: Binds Gq-protein coupled oxytocin receptors on uterine smooth muscle,    |
|      triggering IP3 and intracellular Ca2+ release to produce rhythmic contractions.     |
|    - Dosing: Dilute IV infusion (e.g., 20 to 40 units in 1,000 mL) or IM injection.     |
|    - CRITICAL WARNING: Rapid large IV boluses cause systemic vascular                  |
|      smooth muscle relaxation -> profound systemic hypotension, severe reflex          |
|      tachycardia, myocardial ischemia, coronary vasospasm, and cardiac arrest!          |
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| 2. METHYLERGONOVINE (Methergine) - SECOND-LINE AGENT                                    |
|    - Class: Ergot alkaloid.                                                             |
|    - Mechanism: Partial agonist at alpha-adrenergic, 5-HT2, and dopaminergic receptors. |
|      Induces intense, sustained, tetanic uterine contraction.                           |
|    - Dose: 0.2 mg IM; IV only in emergencies, given slowly over at least 60 seconds.    |
|    - CONTRAINDICATIONS: HYPERTENSION, PREECLAMPSIA/ECLAMPSIA; CAUTION IN CORONARY ARTERY|
|      DISEASE. Causes intense generalized vasoconstriction -> lethal hypertensive        |
|      crisis, intracranial hemorrhage, acute pulmonary edema, and myocardial infarction. |
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| 3. CARBOPROST TROMETHAMINE (Hemabate) - SECOND-LINE AGENT                               |
|    - Class: Synthetic 15-methyl analog of Prostaglandin F2-alpha (PGF2-alpha).          |
|    - Mechanism: Binds prostaglandin FP receptors, stimulating potent myometrial         |
|      contractions and local vascular constriction.                                      |
|    - Dose: 250 mcg (0.25 mg) deep INTRAMUSCULARLY (IM) or intramyometrial; repeat q15-90|
|      min (maximum cumulative dose: 2 mg / 8 doses).                                     |
|    - AVOID IN ASTHMA / REACTIVE AIRWAY DISEASE (relative contraindication). PGF2-alpha  |
|      is a potent bronchial smooth muscle constrictor and can trigger severe            |
|      bronchospasm.                                                                      |
|    - Common Side Effects: Profuse diarrhea, vomiting, nausea, fever/pyrexia, and        |
|      pulmonary hypertension.                                                            |
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Perioperative Adjunctive Pharmacology Summary Reference