Management of Perioperative AKI

1. Risk Stratification and Preoperative Optimization

• Pre-existing CKD, diabetes, heart failure, hypovolemia, older age
• Emergency surgery, cardiac/vascular/aortic procedures, sepsis
• Baseline use of nephrotoxic drugs

• ACE inhibitors/ARBs: Hold for 48 hours before elective cardiac surgery. A meta-analysis of >50,000 procedures linked continuation until the day of surgery with 20% higher mortality and 17% higher AKI rates.
• NSAIDs: Withhold perioperatively - they block prostaglandin-mediated afferent arteriolar dilation, reducing GFR under stress conditions.
• Loop diuretics: Consider holding the day prior; chronic high-dose loop diuretics are linked to postoperative AKI and mortality.
• Statins: Continue perioperatively - patients on statins prior to CABG had lower dialysis and mortality rates in a meta-analysis of 17 studies (>47,000 patients).
• Aminoglycosides/contrast: Use alternatives where possible; if contrast is unavoidable, prehydrate, minimize dose, and withhold other nephrotoxins.

2. Intraoperative Management

Hemodynamic Optimization

• Maintain adequate MAP and cardiac output - the most important modifiable intraoperative factor. Fluctuations in blood pressure directly affect RBF and GFR.
• Abdominal compartment syndrome: Monitor intra-abdominal pressure (via Foley catheter) if fluid overload is suspected. ACS (sustained IAP >20 mmHg) causes a functional prerenal state by reducing abdominal perfusion pressure (MAP - IAP). Prompt decompression is required.
• Avoid sustained hypotension, particularly during cardiac surgery with CPB.

Fluid Management

• Type: Use balanced crystalloids (Lactated Ringer's, Plasma-Lyte) over 0.9% normal saline. The SMART and SALT-ED trials showed balanced crystalloids reduced major adverse kidney events at 30 days vs. normal saline. The chloride load in normal saline reduces renal perfusion via tubuloglomerular feedback.
• Avoid hydroxyethyl starches - eliminated from routine practice after evidence of increased RRT requirement in critically ill/septic patients.
• Amount: Avoid both extremes. The RELIEF trial (3,000 patients, major abdominal surgery) showed a restrictive strategy - while limiting positive balance - increased AKI (8.6% vs. 5.0%) compared to liberal strategy. Excessive restriction is harmful. Goal-directed therapy (GDT) with dynamic monitors (pulse pressure variation, stroke volume variation, esophageal Doppler) is preferable to static CVP-based fluid administration. A meta-analysis of perioperative GDT studies found the most effective AKI reduction came from inotropic support alongside fluid optimization, not fluid alone.

Oxygenation and Hematocrit

• Avoid severe hypoxemia (PaO2 <40 mmHg) - it causes renal vasoconstriction and medullary hypoxia.
• During CPB: hematocrit <20% is associated with AKI; moderate hemodilution (Hct 20-30%) appears renoprotective via reduced viscosity.

Anesthetic Technique

• Neuraxial (epidural/spinal): A systematic review of 107 RCTs showed neuraxial blockade reduced odds of postoperative renal failure by ~30% (CI was wide). Thoracic epidural analgesia is associated with reduced perioperative morbidity including AKI. However, hypotension from high spinal blocks (above T4) must be prevented.
• Sevoflurane/Volatile agents: Despite inorganic fluoride generation and compound A production, sevoflurane is NOT associated with clinical AKI - safe to use.
• Propofol and dexmedetomidine: Both have potential renoprotective anti-inflammatory effects via BMP-7 upregulation. A meta-analysis suggested dexmedetomidine reduces postoperative AKI, though evidence remains preliminary.

3. Nephrotoxin Avoidance

• Fenoldopam, N-acetylcysteine, and sodium bicarbonate have NOT been shown in clinical trials to reduce contrast-associated AKI.
• Mannitol (before aortic cross-clamping) has also failed to show benefit in reducing AKI in clinical trials.
• Low-dose dopamine is not recommended - does not improve mortality despite theoretical vasodilatory effects.

4. Monitoring

• Urine output: Keep >0.5 mL/kg/h - oliguria is an early warning sign, though a brief intraoperative fall is normal.
• Serial creatinine in high-risk patients.
• Intra-abdominal pressure monitoring via Foley catheter if fluid overload or abdominal hypertension is suspected. Bladder pressure >12 mmHg = intra-abdominal hypertension; >20 mmHg with organ dysfunction = ACS.
• Echocardiography (TEE intraoperatively) provides the most direct intravascular volume assessment.

5. Renal Replacement Therapy (RRT)

• Up to 75% of perioperative AKI survivors (including aortic surgery) eventually recover renal function and become dialysis-independent.
• Mode: CRRT (continuous) is preferred for hemodynamically unstable patients; IHD is used in stable patients.

6. Key "Do NOT Do" List

• Do NOT use "renal-dose dopamine" - no mortality benefit
• Do NOT rely on mannitol for renoprotection
• Do NOT use N-acetylcysteine or sodium bicarbonate for contrast nephropathy prevention
• Do NOT use HES (hydroxyethyl starch) fluids
• Do NOT aggressively restrict fluids in major abdominal surgery (RELIEF trial: increased AKI)
• Do NOT use furosemide to convert oliguric to non-oliguric AKI - diuretics do not improve outcomes once AKI is established
• Do NOT continue ACE inhibitors/ARBs until the morning of cardiac surgery

• Miller's Anesthesia, 10e (Chapters 38 and 55)
• Barash Clinical Anesthesia, 9e (Chapter 50)
• Morgan & Mikhail's Clinical Anesthesiology, 7e (Chapter 31)
• RELIEF trial, SMART trial, AKIKI trial, STARRT-AKI trial

Anesthesia in Space

Introduction

1. Physiological Changes in Microgravity Relevant to Anesthesia

A. Cardiovascular System

• Cephalad fluid shift: On entering microgravity, ~1-2 L of fluid shifts from the lower extremities toward the head and thorax, causing facial puffiness, nasal congestion (complicating airway management), and increased central venous pressure initially.
• Plasma volume contraction: Over days-weeks, the body compensates by reducing total plasma volume by 15-20% (hypovolemia), reducing red cell mass, and down-regulating erythropoietin.
• Cardiovascular deconditioning: Progressive reduction in cardiac size, stroke volume, and exercise tolerance (up to 20% decrease). Altered baroreflex sensitivity and systemic vascular resistance.
• Adrenergic receptor changes: Down-regulation of adrenergic receptors impairs the pressor response.
• Clinical implication: High risk of cardiovascular collapse during induction of general anesthesia and positive-pressure ventilation. Orthostatic intolerance affects >80% of ISS crewmembers on return to Earth - this is the most serious cardiovascular complication.

B. Respiratory System

• Tidal volume decreases ~15%, respiratory rate increases ~10% - net minute ventilation maintained.
• Ventilation-perfusion matching actually improves (becomes homogeneous) in microgravity - reduced risk of atelectasis.
• Functional residual capacity and total lung capacity are largely unchanged.
• Nasal congestion (from fluid shift) makes nasal intubation more difficult.

C. Musculoskeletal System

• Bone loss: 1-2% bone mineral density per month, primarily weight-bearing bones. Increases fracture risk during procedures.
• Muscle atrophy: Proximal muscle groups (including respiratory muscles) weaken. Prolonged immobility post-operatively is dangerous.

D. Neuro-vestibular System

• Space motion sickness (SMS) in the first 48-72 hours in up to 70% of astronauts: nausea, vomiting, disorientation. Raises aspiration risk.
• Altered proprioception, spatial disorientation - may affect regional anesthesia positioning and neurological assessment.

E. Pharmacokinetic Changes

• Altered drug distribution: Cephalad fluid shift and reduced plasma volume change volume of distribution.
• Reduced hepatic and renal blood flow (especially during early fluid redistribution) may slow drug metabolism and elimination.
• Muscle atrophy reduces drug binding in muscle compartments.
• Neuromuscular blockers: Altered responses to both depolarizing (succinylcholine - risk with muscle atrophy, hyperkalemia possible in prolonged missions) and non-depolarizing agents due to receptor changes and PK alterations.
• Radiation exposure can damage bone marrow, affecting drug protein binding (reduced albumin).

2. Anesthetic Techniques in Space

A. General Anesthesia - Relatively Unfavorable

• Requires airway instrumentation and controlled ventilation.
• Cardiovascular deconditioning increases risk of profound hypotension at induction.
• Volatile anesthetics pose a major problem: vapors can contaminate the closed cabin atmosphere (the spacecraft is a sealed environment with recirculated air). Vaporizers also behave differently in microgravity (liquid-gas interface disrupted).
• TIVA (Total Intravenous Anesthesia) with propofol and opioids is the preferred approach if GA is required.

B. Regional Anesthesia - Operationally Preferred

• Avoids airway manipulation and systemic drugs.
• Spinal/neuraxial anesthesia: Most attractive option for procedures on extremities, abdomen, perineum.
  • Key uncertainty: Baricity of local anesthetics on Earth relies on gravity to determine spread (hyperbaric agents sink, hypobaric rise). In microgravity, baricity becomes irrelevant - drug spread is unpredictable and may be more extensive or patchy.
  • CSF dynamics are altered (intracranial pressure is raised due to cephalad fluid shift).
  • Spinal geometry changes (paraspinal atrophy, spinal elongation) affect level of block.
  • Risk of high spinal block with hemodynamic collapse in an already cardiovascularly compromised patient.
• Epidural anesthesia: Technically feasible; epidural pressure may be altered.
• Peripheral nerve blocks / local infiltration: Simplest and safest option for limb procedures. Ultrasound guidance preferred. Preferred first-line for minor procedures.

C. Ketamine

• A strong candidate for space anesthesia: causes dissociative anesthesia, preserves airway reflexes and respiratory drive, provides analgesia, maintains hemodynamics (sympathomimetic).
• Can be given IM - useful if IV access is difficult.
• Limitation: emergence phenomena, increases intracranial/intraocular pressure.

3. Airway Management in Microgravity

• Parabolic flight studies (simulated microgravity) have compared airway devices.
• Laryngoscopy and ETT intubation is technically feasible but more difficult due to lack of gravity-assisted positioning and potential nasal congestion.
• LMA/supraglottic devices were found to be as effective or easier to insert than ETT in simulated microgravity - preferred first-line airway in an emergency.
• Combitube has been tested and found reliable in parabolic flight models.
• The "crash" position for intubation cannot be easily achieved without gravity - patient positioning requires restraints.
• Aspiration risk is increased: gastric emptying is delayed in microgravity, and SMS-related vomiting is common. All patients should be treated as full stomach (RSI approach).

4. Equipment Constraints and Logistics

5. Monitoring

• Standard monitoring (SpO2, NIBP, capnography, ECG) is achievable in miniaturized form.
• Capnography is essential as clinical assessment (chest rise) is unreliable in microgravity.
• Point-of-care ultrasound (POCUS) is increasingly used on the ISS and is a key skill.
• Neuromuscular monitoring is important given altered NMB pharmacology.

6. Post-Operative Considerations

• Immobilization post-surgery accelerates muscle atrophy and bone loss - early mobilization critical.
• Pain management: IV/IM opioids, peripheral nerve blocks preferred. NSAIDs may mask inflammatory responses.
• DVT prophylaxis: already increased risk in microgravity due to altered venous return and immobility.
• Wound healing may be impaired due to immune dysregulation and radiation effects.
• Rehabilitation is severely limited in the spacecraft environment.

Summary Table

Conclusion