Anesthesia

TIVA: induction AND maintenance of general anaesthesia using only intravenous drugs, without any inhalational anaesthetic agent; requires at least three pharmacological components:

Hypnotic agent (produces unconsciousness): propofol (almost universally); alternatives: thiopentone, ketamine, dexmedetomidine as adjuncts

Analgesic agent (blunts surgical pain response): remifentanil (preferred — ultra-short context-sensitive half-time, titrable); alternatives: fentanyl, alfentanil, ketamine Neuromuscular blocking agent (facilitates intubation and surgical relaxation, if required): rocuronium, vecuronium, cisatracurium

Component Target Concentration Effect Rationale

Propofol Induction: 4–6 mcg/mL Ce Unconsciousness, amnesia; Dose-dependent reduction of CMRO₂ and CBF (neuroprotective); lowest PONV (Schnider); Maintenance: 3–4 mild muscle relaxation at incidence of all agents; no HPV inhibition; environmentally clean; predictable recovery mcg/mL Ce (surgery); higher concentrations; with TCI

Sedation: 1–1.5 mcg/mL Ce antiemetic at subanaesthetic concentrations

Remifentanil Blunt intubation response: 4– Analgesia; suppression of Unique organ-independent ester hydrolysis metabolism → context-sensitive half-time = 8 ng/mL; Maintenance: 2–5 haemodynamic response to 3 min regardless of infusion duration; no drug accumulation; predictable emergence ng/mL (depending on surgical stimulation; reduces even after 12-hour infusion; CRITICAL: provide post-op analgesia (morphine/NSAIDs) stimulation); Emergence: propofol requirement by 30– before stopping remifentanil as its analgesic effect disappears within 5–10 min of reduce to 1–2 ng/mL 40% stopping

Unlike volatile anaesthesia (where ETCO₂ confirms drug delivery and MAC multiples correlate with depth), TIVA has no exhaled gas indicator of delivery or depth — processed EEG monitoring is essential

BIS (Bispectral Index): 0–100 scale; target 40–60 for surgical anaesthesia; values <40 suggest excessive depth (burst suppression); >60 → inadequate depth and awareness risk; specifically validated for propofol and volatile agents

Entropy (Spectral Entropy): State Entropy (SE) and Response Entropy (RE); similar utility to BIS; uses different mathematical processing of the EEG spectrum pEEG (Patient-State Index, Narcotrend): alternative processed EEG monitors; similar principle to BIS

Important limitation: all processed EEG monitors fail to reliably predict awareness in the concentration range where awareness most commonly occurs (0.2– 0.4 MAC equivalent of propofol); they provide a trend indicator, not an absolute guarantee of unconsciousness

Advantage Clinical Basis Lowest PONV incidence Propofol has intrinsic antiemetic properties (5-HT3 antagonism at sub-anaesthetic concentrations); absence of volatile agents (which are emetogenic); absence of N₂O; TIVA reduces PONV by ~25–30% vs inhalational techniques No HPV inhibition Propofol does not inhibit hypoxic pulmonary vasoconstriction (unlike volatile agents) → superior oxygenation during one-lung ventilation; preferred for thoracic anaesthesia No MH triggering Propofol and opioids are safe in MH-susceptible patients; TIVA is mandatory when volatile agents are contraindicated (MH, suspected MH susceptibility) No operating room No volatile agent exhaled into the OR environment; protects OR staff from chronic low-level anaesthetic exposure pollution Environmental No halogenated greenhouse gas emissions; environmentally superior to all volatile agent techniques sustainability Predictable recovery with Remifentanil's flat CSHT (3 min) means recovery time is independent of infusion duration; propofol's moderate CSHT rises slowly — propofol-remifentanil suitable for even very long cases (8+ hours) with predictable emergence Suitable for remote TIVA requires only a syringe pump and IV access — no anaesthetic machine, vaporizer, or gas supplies needed; ideal for MRI (no locations ferromagnetic components), remote sites, transport anaesthesia

Definition: BCIS is defined as hypoxia (SpO₂ fall >10% from baseline), hypotension (systolic BP fall >20% from baseline), or both, occurring at the time of cementation, prosthesis insertion, reduction of the joint, or deflation of a tourniquet during orthopaedic surgery using PMMA bone cement Grade Clinical Features Incidence Mortality Grade 1 Moderate hypoxia (SpO₂ fall >10%) OR moderate hypotension (systolic BP Common — up to 30% Near-zero direct mortality (Mild) fall >20%) — not both; brief, self-limiting of cemented THRs Grade 2 Severe hypoxia (SpO₂ <94%) AND/OR severe hypotension (systolic BP fall ~5–10% Low but non-trivial; associated with increased (Moderate) >40%) AND/OR unexpected loss of consciousness postoperative complications Grade 3 Cardiovascular collapse requiring cardiopulmonary resuscitation — cardiac ~0.5–1% of cemented Very high — approaching 100% in full cardiac (Severe) arrest THRs arrest without immediate CPR

Risk Factor Specific Risk Factors Category Patient Advanced age (>70 years — greater intramedullary fat content, more fragile vasculature); male sex (larger intramedullary cavities); pre-existing factors cardiorespiratory disease (impaired ability to compensate for acute pulmonary embolism); PFO (paradoxical embolism risk); hypovolaemia at time of cementation; pathological bone (osteoporosis, Paget's, metastatic disease — more intramedullary blood and fat, more friable); pulmonary hypertension (reduced reserve for additional right ventricular afterload) Surgical Cemented implant (vs cementless — cementless arthroplasty does not cause BCIS); revision surgery (larger canals, more debris); long-stem prostheses factors (greater medullary surface area → more material driven into veins); inadequate canal cleaning before cementation (more marrow content → more embolic material); cement pressurisation technique; cement mixing (higher monomer content with improper mixing) Anaesthetic Hypovolaemia at time of cementation (reduced cardiac reserve for haemodynamic response); inadequate preloading; general anaesthesia reduces factors cardiovascular reserve vs regional; the haemodynamic challenge of BCIS may be tolerated better under spinal/epidural anaesthesia (better maintained cardiovascular reserve in spinal vs GA)

Preventive Measures

Communication: surgeon must verbally announce BEFORE cementation — "I am about to cement" — this is a mandatory communication point; the anaesthesiologist must be at full vigilance at the critical moment

Pre-cementation fluid loading: ensure the patient is euvolaemic or mildly hypervolaemic before cement is introduced; a small preloading fluid bolus (250–500 mL crystalloid) 5–10 minutes before cementation ensures adequate intravascular volume to buffer the haemodynamic response

FiO₂ to 1.0: increase to 100% O₂ immediately before cementation is announced; this maximises the oxygen reservoir in the FRC to buffer any hypoxic episode

ETCO₂ monitoring: a sudden fall in ETCO₂ is an early sign of massive embolism (reduced pulmonary blood flow → reduced CO₂ delivery to alveoli → ETCO₂ falls); warns the anaesthesiologist before SpO₂ falls

Surgical technique: thorough canal lavage (irrigation before cementation removes loose marrow and blood); use of cement restrictors (reduces the intramedullary volume receiving cement pressure); retrograde cementing technique (fills the canal from distal to proximal — minimises air entrapment); venting holes drilled by surgeon (releases intramedullary pressure) Management of Cardiovascular Collapse (Grade 3 BCIS)

Principle Application to End-of-Life Care Autonomy The patient's right to refuse or accept treatment, including life-sustaining measures; expressed through informed consent, advance directives (living will, healthcare proxy), and verbal refusal; must be respected even when the clinician disagrees with the patient's decision; a competent adult's refusal of CPR or ventilation is legally and ethically binding Beneficence Act in the patient's best interest; in end-of-life care, this requires understanding what constitutes "best interest" beyond mere prolongation of biological function — quality of life, freedom from suffering, dignity, and the patient's own values determine best interest Non- "First, do no harm" — in end-of-life care, this principle supports withholding treatments that produce suffering without meaningful benefit; continuing maleficence painful, invasive treatments in a terminally ill patient who cannot benefit is a form of harm; overly aggressive treatment at the end of life violates nonmaleficence Justice Fair allocation of resources; when ICU resources are limited, justice requires that they be directed toward patients who can benefit; withdrawing futile ICU care also has a justice dimension — freeing resources for patients who can meaningfully benefit Doctrine of An action that is intended for a good purpose (relieving pain/suffering) but has a known adverse side effect (possibly hastening death from respiratory

Double depression) is ethically permissible if: the action itself is not inherently wrong; the bad effect is foreseen but not intended; the good effect outweighs the Effect bad; this principle underpins the use of opioids and sedation for palliative purposes even when there is a theoretical risk of respiratory depression

Definition: a DNR/DNAR order is a specific medical order instructing healthcare providers not to perform CPR (cardiopulmonary resuscitation) in the event of cardiac or respiratory arrest; it does NOT mean withdrawal of all treatment — it only refers to CPR attempts

Indications for DNR discussion: terminal malignancy with no curative treatment; advanced end-organ failure (GOLD IV COPD, NYHA IV heart failure, ESRD); severe neurological injury (persistent vegetative state, brainstem death); patient's own expressed wish to avoid CPR; clinical judgment that CPR would be futile or cause more harm than benefit

Perioperative DNR — the anaesthesiologist's challenge: a patient with a pre-existing DNR order who requires surgery for quality-of-life purposes (pain relief, obstruction relief) presents a specific ethical dilemma; the anaesthesiologist does not automatically suspend the DNR during surgery; the standard approach is: Pre-operatively discuss the DNR order with the patient/family and surgeons

The patient has three options: (1) suspend the DNR during the perioperative period (the resuscitation risks of anaesthesia and surgery justify temporary DNR suspension); (2) require procedure-directed DNR (only resuscitate for anaesthesia-caused arrests, not disease-related arrests); (3) retain DNR in full (no resuscitation for any cause) Document the agreed modification clearly in the notes before proceeding

Legal status in India: there is no specific statute governing DNR orders in India; the Supreme Court of India judgment (Common Cause vs Union of India, 2018) affirmed the right to die with dignity and the validity of advance medical directives (living wills); hospitals are expected to develop policies aligned with this ruling; end-of-life orders should be documented clearly, reviewed with families, and counter-signed by senior medical staff

Ethical basis: withholding and withdrawing futile treatment are ethically equivalent; prolonging life with no prospect of meaningful recovery is not a benefit to the patient; WLST is not "killing" the patient — it is removing an impediment to natural death; the patient dies of their underlying disease, not from the withdrawal Decision process (ICU):

Senior clinician assessment: confirm that treatment is futile (no prospect of recovery to a quality of life the patient would value, based on clinical evidence and the patient's expressed values)

Family meeting: structured, compassionate communication with the family/surrogate decision-maker; explain the clinical situation honestly; establish what the patient would have wanted; allow time for family to process; avoid false hope without being brutal

Multidisciplinary agreement: consensus from the treating intensivist, nursing team, relevant specialists, and chaplaincy/social work if appropriate; document the decision clearly in the notes

Ethical committee consultation: for difficult cases or family disagreement; not required for straightforward clinical decisions where family and clinical team agree

Process of withdrawal: ensure comfort medications are in place BEFORE withdrawal (morphine infusion, midazolam infusion — titrate to comfort, not to hasten death); then remove ventilator support gradually or extubate; family may be present; provide dignified, peaceful environment; post-withdrawal monitoring for comfort (pain, dyspnoea, agitation) and adjustment of medications; notify death and complete documentation; provide family support

Concept Definition Ethical Status Palliative The use of sedative drugs to reduce consciousness in patients with terminal illness and refractory Ethically permissible under the doctrine of sedation suffering — symptoms that cannot be adequately controlled by any other means (pain, dyspnoea, double effect; legally supported in India and agitation, existential distress); the goal is relief of suffering, not hastening of death; depth of sedation most jurisdictions; distinct from euthanasia ranges from mild (rousable) to deep (unconscious) (where the intent is to end life) Euthanasia Deliberate administration of a lethal drug specifically intended to end the patient's life; NOT the same as Illegal in India; ethical debate ongoing globally; palliative sedation; NOT legal in India or most countries NOT part of anaesthesia/ICU practice in India Physician- Physician prescribes a lethal drug that the patient self-administers; NOT legal in India Illegal in India; legal in Netherlands, Belgium, Assisted Canada, Oregon (USA) Suicide (PAS)

Drugs for palliative sedation: midazolam (most common — 1–10 mg/hr SC or IV infusion); morphine (for pain and dyspnoea — primary analgesic with titration; not intended as the sedating agent); phenobarbitone (for seizures or refractory agitation in terminal patients); propofol (for deeply distressing cases requiring rapid sedation in inpatient palliative/ICU settings); combination midazolam + morphine most commonly used Anaesthesiologist's specific role: expertise in drug titration and pharmacology; experienced in airway management (relevant if sedation produces airway compromise); able to manage the physiological consequences of advanced disease; liaison between the palliative team and ICU; providing terminal sedation when palliative care team requests specialist support for difficult symptom control

Feature Acute Pain Chronic Pain Duration <3 months; recent onset; expected to resolve as tissue heals Persists >3 months; beyond expected healing time; often persists after original injury has healed

Biological Adaptive — warns of tissue damage; promotes protective Maladaptive — no longer serves a protective purpose; becomes a disease in its own purpose behaviour (rest, seeking care); essential for survival right ("chronic pain syndrome") Neurobiology Nociceptive signals from tissue damage → ascending pain Central sensitisation; neuroplastic changes in the dorsal horn and brain; descending pathways → cortical pain perception; proportional to damage inhibitory pathway failure; pain independent of (or out of proportion to) peripheral stimulus Treatment Treat underlying cause; multimodal analgesia; short-term Biopsychosocial model; multidisciplinary team; minimise opioid exposure; focus on approach opioids acceptable function not pain elimination

Type Mechanism Characteristics Examples Treatment Nociceptive Activation of A-delta (sharp, fast pain) and C Well-localised; proportional to stimulus; Bone pain, muscle pain, NSAIDs; — Somatic fibres (slow, burning pain) in somatic tissues improves with rest and analgesics; described incisional pain, trauma paracetamol; by noxious stimuli (mechanical, thermal, as sharp, aching, throbbing; responds to opioids; regional chemical) — signalling to the dorsal horn → NSAIDs and opioids blocks thalamus → somatosensory cortex Nociceptive Activation of visceral afferents by distension, Poorly localised; colicky or pressure-like; Bowel obstruction, biliary Opioids; N-butyl — Visceral ischaemia, or inflammation of hollow organs; associated with autonomic responses (nausea, colic, ureteric colic, scopolamine travels via sympathetic nerves; referred pain sweating, pallor); referred to somatic areas cardiac ischaemia (antispasmodic); via shared dermatomes with somatic fibres (e.g., MI → left arm pain; appendicitis → treat underlying periumbilical then RIF) cause Neuropathic Initiated or caused by a primary lesion or Burning, shooting, electric shock-like, tingling Diabetic peripheral Gabapentinoids disease in the somatosensory nervous system (dysaesthesia); allodynia (pain from normally neuropathy, post-herpetic (pregabalin, (peripheral or central); pathological changes in non-painful stimulus — light touch causes neuralgia, phantom limb, gabapentin); TCAs neural signalling — ectopic discharge from severe pain); hyperalgesia (exaggerated pain complex regional pain (amitriptyline); injured axons, central sensitisation, loss of response to painful stimulus); often associated syndrome (CRPS), SNRIs (duloxetine); descending inhibitory control, glial activation with sensory deficit in the painful area; often chemotherapy-induced, topical poorly responsive to NSAIDs/opioids post-surgical (chronic lidocaine/capsaicin; post-surgical pain) nerve blocks; spinal cord stimulation Nociplastic Altered nociception from changed functioning Widespread, diffuse pain; poor correlation with Fibromyalgia; irritable Exercise; cognitive (Central of the somatosensory nervous system without tissue findings; associated with fibromyalgia, bowel syndrome; tension- behavioural therapy Sensitisation) clear evidence of actual tissue damage or irritable bowel, tension headache; fatigue; type headache; (CBT); SNRIs nerve damage; the pain is real but arises from sleep disturbance; often has psychological widespread (duloxetine); TCAs; a sensitised central nervous system (changes comorbidities musculoskeletal pain low-dose naltrexone in dorsal horn transmission, supraspinal (experimental); processing, descending modulation) multidisciplinary rehabilitation

The Biopsychosocial Model — Framework for All Interventions The biopsychosocial model (Engel, 1977) recognises that chronic pain is determined by three interacting dimensions: biological (tissue pathology, neural sensitisation, genetics, pharmacology), psychological (depression, anxiety, catastrophising, fear-avoidance behaviour, sleep disturbance), and social (employment, social support, compensation claims, cultural attitudes to pain); effective chronic pain management must address all three dimensions simultaneously Component Interventions Evidence Level 1. Step 1 (mild pain): paracetamol 500–1000 mg QID; NSAIDs (ibuprofen, naproxen, celecoxib) — WHO analgesic ladder (adapted for chronic Pharmacological most evidence for acute/inflammatory pain; limit <10 days; GI/renal/cardiovascular risk monitoring pain); NICE guidelines (NG173); NNT for

Step 2 (moderate pain): weak opioids (codeine, tramadol) + step 1; tramadol (SNRI + opioid) neuropathic agents: duloxetine NNT 6.5; particularly useful for neuropathic pain; gabapentinoids (pregabalin 75–300 mg BD; gabapentin 300– pregabalin NNT 7.7; amitriptyline NNT 6.4 1200 mg TID) for neuropathic

Step 3 (severe/neuropathic): strong opioids (morphine, oxycodone, fentanyl patch) — ONLY for chronic pain with demonstrated benefit and documented risk-benefit discussion; buprenorphine patches (7-day) — less euphoric, ceiling effect, suitable for chronic pain; duloxetine 60–120 mg OD (SNRI with level 1 evidence for diabetic neuropathy, fibromyalgia, MSK pain); amitriptyline 10–75 mg nocte (low-dose TCA — analgesic, sleep aid, also antidepressant) 2. Interventional Nerve blocks: diagnostic and therapeutic; e.g., coeliac plexus block (pancreatic cancer pain), NICE (NG59) — SCS for FBSS and CRPS; / Procedural stellate ganglion block, sympathetic blocks level 1 evidence for SCS in selected

Epidural steroid injection: lumbar radiculopathy, cervical radiculopathy — reduces nerve root populations; RFA supported by multiple inflammation; short-to-medium term benefit RCTs for facet pain

Radiofrequency ablation (RFA): thermal or pulsed RFA of facet joint medial branches for chronic facet pain; cryoablation of sensory nerves

Spinal Cord Stimulation (SCS): implanted lead in the dorsal epidural space; dorsal column electrical stimulation produces paresthesia overlying the painful area; excellent evidence for CRPS, failed back surgery syndrome (FBSS), refractory angina; NNT ~2.4 for CRPS

Intrathecal drug delivery (ITDD) systems: implanted pump delivering opioids/baclofen/ziconotide directly into the CSF; for cancer pain or spasticity; reduces systemic opioid requirements

TENS (Transcutaneous Electrical Nerve Stimulation): surface electrodes; modulates pain via gate control theory (large-fibre stimulation closes the gate to C-fibre transmission); simple, noninvasive; evidence moderate but patient-driven 3. Psychological Cognitive Behavioural Therapy (CBT): the most evidence-based psychological treatment for Cochrane reviews: CBT reduces pain chronic pain; addresses catastrophising, fear-avoidance, maladaptive pain behaviours; teaches intensity (SMD −0.4) and disability (SMD coping strategies, activity pacing, relaxation; delivered individually or in group settings; best evidence −0.3) in chronic low back pain; psychological for fibromyalgia, CLBP, headache; NNT ~3–5 for significant improvement in disability interventions are NICE-recommended as

Acceptance and Commitment Therapy (ACT): focuses on accepting pain rather than eliminating it; core components of chronic pain increasing psychological flexibility; newer evidence base but growing; particularly useful in patients management where pain cannot be eliminated

Mindfulness-Based Stress Reduction (MBSR): 8-week structured programme; meditation, body scan, yoga; reduces pain catastrophising and improves quality of life; level 2 evidence for chronic pain

Pain neuroscience education (PNE): teaching patients the neuroscience of pain processing reduces catastrophising and improves outcomes; shifts the patient's conceptual model from "pain = damage" to "pain = overactive alarm system" 4. Physical / Exercise therapy: the single most evidence-based physical intervention for chronic pain; aerobic Cochrane reviews: exercise vs no treatment Rehabilitative exercise, resistance training, and specific exercise programmes (e.g., McKenzie for CLBP, graded for CLBP — moderate quality evidence for activity); mechanisms include endorphin release, central sensitisation reversal, anti-inflammatory improved pain and function; exercise is NICE effects; supervised exercise superior to home exercise first-line recommendation for CLBP

Physiotherapy: manual therapy (mobilisation, manipulation) for musculoskeletal pain; specific exercise prescription; postural correction

Hydrotherapy: warm water exercises reduce joint loading while allowing mobility; excellent for fibromyalgia, OA, rheumatoid arthritis

Occupational therapy: activity grading, adaptive devices, return-to-work planning; particularly for patients with chronic pain and disability

Cardiac Output (CO): the volume of blood ejected by the left ventricle per minute; CO = Stroke Volume (SV) × Heart Rate (HR); normal = 4–8 L/min; Cardiac Index (CI) = CO/BSA; normal CI = 2.5–4.0 L/min/m²

Stroke Volume (SV): the volume ejected per beat (normal 60–100 mL); determined by preload, afterload, and contractility; SV variation (SVV) and pulse pressure variation (PPV) are dynamic indices of preload responsiveness in mechanically-ventilated patients — if SVV >13% or PPV >13%, the patient is likely preload-responsive (will increase SV with fluid challenge) Most non-invasive monitors estimate CO or SV indirectly through physical principles (thermodilution, Fick, bioreactance, Doppler) — each with its own assumptions, limitations, and sources of error

Accuracy vs Method / Device Principle Invasiveness Key Advantages Key Limitations PAC Oesophageal A flexible probe (6 mm) placed in the Minimally Good Real-time continuous; the Requires intubation and Doppler Monitor oesophagus at the level of the invasive — concordance most validated non-PAC CO sedation; operator skill for (ODM) — CardioQ descending thoracic aorta; emits requires with PAC (bias monitor; FTc provides probe positioning; not continuous Doppler ultrasound at 4 MHz; intubated/sedated within ±20%); unique stroke volume index reliable in AF (irregular measures red blood cell velocity in the patient; placed validated in and preload assessment; stroke volumes); descending aorta → waveform analysis like NGT; not multiple large OPTIMISE trial showed overestimates CO if probe provides stroke volume, corrected flow possible in awake trials ODM-GDT reduces not correctly aligned with time (FTc), and cardiac output estimate; patients or with complications in major aortic blood flow; only assumes a fixed proportion of CO passes oesophageal surgery; NICE-approved measures CO indirectly through the descending aorta (roughly pathology (MTG3) for use in major (assumes fixed descending 70%) surgery aorta fraction) Pulse Contour Analyses the arterial pressure waveform Minimally Moderate Continuous real-time CO; Accuracy degrades

Analysis — to calculate stroke volume from the area invasive — concordance also provides SVV and PPV significantly with arterial PiCCO, LiDCO, under the systolic portion of the pressure requires arterial with PAC; (fluid responsiveness waveform distortion FloTrac/Vigileo wave; requires an arterial line (radial or line (standard accuracy indices); PiCCO additionally (vasopressors, arrhythmia, femoral); some systems require anaesthetic decreases in: provides extravascular lung vasoconstriction); intermittent external calibration (PiCCO monitoring); no high-dose water and intrathoracic calibrated systems need uses transpulmonary thermodilution; additional central vasopressors, blood volume; suitable for periodic recalibration LiDCO uses lithium dilution); venous access irregular rhythms major surgery and ICU; (position change, FloTrac/Vigileo uses a proprietary needed for (AF), severe FloTrac requires only a haemodynamic instability); algorithm based on patient demographics FloTrac; PiCCO peripheral standard arterial line FloTrac less accurate than without external calibration and LiDCO vasoconstriction, calibrated systems in require calibration cardiac haemodynamically bolus arrhythmias, unstable patients aortic regurgitation Thoracic Alternating electrical current is passed Non-invasive — Moderate Completely non-invasive — Lower accuracy than ODM Electrical through the thorax via surface electrodes surface concordance no needles; suitable for or calibrated pulse contour Bioimpedance / on the neck and chest; changes in electrodes; no with PAC in non-intubated patients; can in high acuity; affected by Bioreactance transthoracic impedance (related to the arterial line stable patients; monitor awake patients in patient movement (NICOM, Cheetah) aortic blood volume change with each required; fully poor accuracy in: ICU or stepdown; useful for (artefact); unreliable in heartbeat) are used to calculate SV; non-invasive obesity, trend monitoring pulmonary oedema, severe bioreactance (NICOM) measures the cardiac pulmonary obesity, thoracic surgery phase shift of the AC signal rather than monitoring oedema (fluid patients amplitude — more specific to aortic flow, alters less affected by pleural fluid or body impedance), composition arrhythmias, after cardiac surgery (altered thoracic anatomy and fluid) Transoesophageal A phased-array ultrasound transducer on Minimally Excellent Provides qualitative AND Requires intubated patient; Echocardiography an oesophageal probe; provides direct invasive — accuracy when quantitative data; directly needs formal training (TOE/TEE) imaging of cardiac chambers, valves, and requires performed by a visualises the cause of (BSE/EACVI TOE great vessels; SV calculated from the intubation and competent haemodynamic instability accreditation); not portable velocity-time integral (VTI) of the LVOT sedation; operator; (tamponade, LV/RV or continuously available in Doppler multiplied by the LVOT cross- operator considered a dysfunction, hypovolaemia, all settings; time-intensive sectional area (2D echo measurement); expertise reference PE, valve per measurement; relative provides the gold standard for direct required; requires standard for regurgitation/stenosis); contraindications visualisation of cardiac function, wall formal TOE perioperative cannot be replicated by any (oesophageal disease, motion, pericardial effusion, and competency haemodynamics; other non-invasive monitor; variceal bleeding risk) haemodynamic instability training limited not by provides wall motion (EACVI/ASE accuracy but by assessment for ischaemia accreditation) operator skill and detection access Non-Invasive Continuous non-invasive blood pressure Non-invasive — Moderate Completely non-invasive; Accuracy reduced by Haemodynamic measurement from a finger cuff using the finger cuff; accuracy for suitable for monitoring in peripheral vasoconstriction; Monitor (CNAP — volume clamp method (Finapres suitable for trending; may awake patients, procedural requires regular calibration continuous non- technology); uses the continuous BP awake patients underestimate in sedation, obstetrics (non- cycles; less accurate than invasive arterial waveform to compute CO via pulse peripheral invasive BP + CO), arterial line-based systems pressure + Nexfin) contour analysis; completely non-invasive vasoconstriction monitored care settings in haemodynamically — finger cuff only and overestimate unstable patients in warm vasodilated patients

Concept: GDT uses real-time CO/SV monitoring to guide fluid and vasopressor therapy toward specific haemodynamic targets — aiming to optimise oxygen delivery (DO₂) to tissues rather than simply normalising conventional vital signs (MAP, HR, urine output); key targets: CO/CI, SV, SVV/PPV (fluid responsiveness), and derived DO₂ OPTIMISE Trial (Pearse et al., BMJ 2014; n=734): high-risk major gastrointestinal surgery patients randomised to ODM-guided GDT vs standard care; GDT group received targeted colloid boluses to maximise SV and maintain FTc 35–40 ms; GDT significantly reduced postoperative complications (44.3% vs 51.0% — adjusted risk ratio 0.84) — the largest pragmatic RCT of CO-guided therapy in major surgery

Fluid responsiveness assessment: SVV >13% (mechanically-ventilated patients in sinus rhythm) or a passive leg raise (PLR) test predicts fluid responsiveness; if fluid responsive → 250 mL crystalloid/colloid bolus → reassess SV; if SV increases >10% → repeat; if SV increase <10% → patient is on the flat part of the Frank-Starling curve → additional fluid will not increase SV → use vasopressors instead

During third stage of labour, the placenta separates and the uterus must contract rapidly to compress the spiral arteries of the placental bed — these arteries supply the placenta at a rate of approximately 500 mL/min at term; without uterine contraction, these open vessel sinuses bleed at this rate, producing potentially fatal haemorrhage within minutes Normal uterine contraction is mediated by oxytocin (from the posterior pituitary) acting on uterine myocyte oxytocin receptors → intracellular Ca²⁺ → myosin light chain kinase activation → smooth muscle contraction; prostaglandins (PGE₂, PGF₂α) and ergometrine (α-adrenergic stimulation + 5-HT-mediated) independently support uterine tone

Atony occurs when: oxytocin receptor downregulation (from prolonged IV oxytocin during labour); myometrial fatigue (prolonged labour, grand multiparity); mechanical failure to contract (fibroids, distension from polyhydramnios, multiple gestation, macrosomia); retained placental tissue preventing uniform contraction; drug-induced uterine relaxation (volatile anaesthetic agents, magnesium sulphate, tocolytics, nifedipine)

T Category Specific Risk Factors

T1 — Uterine atony Grand multiparity (≥5 deliveries — exhausted myometrium); overdistended uterus (multiple pregnancy, polyhydramnios, macrosomia —

TONE — failure of LGA baby >4 kg); prolonged labour (myometrial fatigue); precipitate labour; induction/augmentation with oxytocin (receptor uterine downregulation); uterine fibroids (prevent uniform contraction); general anaesthesia with volatile agents (dose-dependent uterine muscle to relaxation); magnesium sulphate infusion (tocolytic); chorioamnionitis contract

T2 — Retained Retained placenta or placental fragments (prevents normal uterine retraction and contraction); succenturiate lobe (accessory lobe — TISSUE products of frequently retained); placenta accreta spectrum (accreta/increta/percreta — placenta abnormally adherent, cannot separate normally; conception major risk for catastrophic PPH); placenta praevia (abnormally located, prevents normal third stage)

T3 — Genital tract Cervical tears (especially after rapid delivery); vaginal lacerations; perineal tears (1st–4th degree); uterine rupture (rare but catastrophic); TRAUMA lacerations uterine inversion (fundus turns inside out — rare; causes profound haemorrhage and shock); episiotomy; forceps/ventouse delivery; and injuries caesarean incision extension

T4 — Coagulopathy Pre-existing coagulopathy (ITP, vWD, haemophilia carrier); obstetric causes of coagulopathy: abruptio placentae (DIC from thromboplastin THROMBIN release), amniotic fluid embolism (DIC), HELLP syndrome, pre-eclampsia; dilutional coagulopathy from massive transfusion; anticoagulant therapy (LMWH, warfarin)

OP compound (lipid-soluble; absorbed via skin, inhalation, ingestion, conjunctiva) → covalently phosphorylates the serine hydroxyl group at the active site of acetylcholinesterase (AChE) → AChE is IRREVERSIBLY INHIBITED → cannot hydrolyse acetylcholine (ACh) at cholinergic synapses → ACh accumulates at: (1) all parasympathetic postganglionic nerve-effector junctions (muscarinic receptors); (2) nicotinic receptors at the NMJ (skeletal muscle); (3) autonomic ganglia — sympathetic and parasympathetic (nicotinic ganglionic receptors); (4) CNS synapses (muscarinic and nicotinic receptors in brain and spinal cord) → prolonged, excessive stimulation of ALL cholinergic receptors simultaneously → the CHOLINERGIC CRISIS.

SLUDGE (Muscarinic) = Salivation, Lacrimation, Urination, Defecation, GI cramps/Emesis DUMBELS = Defecation/Diarrhoea, Urination, Miosis, Bradycardia/Bronchospasm/Bronchorrhoea, Emesis, Lacrimation, Salivation System Receptor Features Mnemonic Aid MUSCARINIC M1, M2, Salivation (excessive drooling), Lacrimation (tearing), Urination (incontinence), Defecation (diarrhoea), GI SLUDGE + DUMBELS; (parasympathetic M3 cramps, Emesis; ADDITIONALLY: MIOSIS (pinpoint pupils — pathognomonic), bradycardia, "wet and small" — nerve-effector receptors bronchospasm, BRONCHORRHOEA (copious secretions in airways — the most life-threatening feature), excessive secretions + junctions) hypotension, diaphoresis, urinary incontinence miosis NICOTINIC (NMJ N1 NMJ stimulation → initial FASCICULATIONS (visible muscle twitching — brief initial stimulation phase) → "Paralysis follows + autonomic (ganglionic) progressing to PARALYSIS (continuous receptor depolarisation → end-plate depolarisation block → fasciculations" — never ganglia) and N2 flaccid paralysis); diaphragm paralysis → respiratory failure (the primary cause of death); GANGLIONIC use succinylcholine (NMJ) stimulation → tachycardia (may coexist with or override bradycardia), hypertension (early), pallor, (pseudocholinesterase receptors mydriasis (may counteract or compete with muscarinic miosis) inhibited → prolonged paralysis) CNS Central Anxiety, restlessness, delirium, seizures (classically intractable — resistant to standard anticonvulsants "Seizures + coma" — muscarinic alone; require benzodiazepines + atropine for adequate control); coma; central respiratory depression CNS cholinergic storm and (compounding NMJ paralysis); in severe poisoning, all three mechanisms combine to produce apnoea nicotinic receptors

Grade Clinical Features Management Mild Alert; salivation, lacrimation, miosis, diarrhoea; RR normal; no Observation; atropine titration; supportive respiratory compromise Moderate Confusion; significant bronchorrhea, bronchospasm; mild respiratory ICU admission; IV atropine; pralidoxime; monitor RR closely — may deteriorate distress; RR increased; fasciculations prominent rapidly Severe Coma; seizures; severe bronchorrhoea and bronchospasm; respiratory Immediate intubation + mechanical ventilation; IV atropine titration; pralidoxime; failure (apnoea); bradycardia + hypotension; paralysis benzodiazepines for seizures; ICU; prolonged ventilatory support

PERSONAL PROTECTION FIRST: OP compounds are highly lipid-soluble and absorbed through skin; all healthcare staff must wear gloves, gown, and eye protection before approaching the patient; remove and bag the patient's contaminated clothing before they enter the department

Decontamination: thorough washing of all exposed skin surfaces with soap and water (for 10–15 minutes) if dermal exposure; flush eyes with saline for conjunctival exposure; in ingestion cases: gastric lavage via NGT (within 1 hour of ingestion) + activated charcoal 50 g via NGT (if airway protected); emesis is CONTRAINDICATED (risk of aspiration, and rapid loss of consciousness)

Mechanism: pralidoxime (PAM; 2-PAM chloride) is an oxime compound that attacks the OP-AChE bond BEFORE ageing occurs → reactivates AChE by removing the OP group from the serine active site → restored AChE can resume hydrolysing ACh; this specifically reverses the NMJ (nicotinic) effects of OP poisoning (reverses fasciculations and paralysis) in addition to reducing the ACh burden at muscarinic synapses

Critical timing: pralidoxime MUST be given BEFORE AGEING; ageing rate depends on the specific OP compound — for most pesticide OPs, ageing occurs over hours; give pralidoxime as soon as diagnosis is made (ideally within 6–12 hours for most pesticides)

Dose: 1–2 g IV over 15–30 minutes; then 200–500 mg/hr infusion for 24–48 hours; continue until patient is asymptomatic and off atropine

Controversy: a large RCT from Sri Lanka (Eddleston et al., Lancet 2009) showed no mortality benefit of pralidoxime in agricultural OP poisoning — ongoing debate about its clinical utility in pesticide poisoning; still recommended in WHO and Indian guidelines; most useful early, before ageing

Seizures: benzodiazepines (diazepam 10 mg IV or midazolam 5–10 mg IV) — first-line; phenytoin is relatively ineffective for OP seizures (which are cholinergic in origin); continue until seizures stop

Monitor: ECG (QT prolongation from OP toxicity + atropine; AF, VT); blood glucose (OP poisoning causes hyperglycaemia from glycogen mobilisation); RBC cholinesterase activity (reflects AChE inhibition — correlates with severity); plasma cholinesterase (pseudocholinesterase — also inhibited but recovers faster)

Parameter Definition Clinical Meaning Volume of The apparent volume into which a drug distributes to produce the observed Large Vd → drug distributes extensively into peripheral tissues →

Distribution plasma concentration: Vd = Dose / Cp; expressed in L or L/kg smaller plasma concentration for a given dose → longer elimination half(Vd) life; e.g., propofol Vd ~200–500 L (large — distributes into fat widely) Clearance Volume of plasma cleared of drug per unit time (mL/min or L/hr); CL = Dose / High clearance → drug eliminated rapidly from plasma → short duration; (CL) AUC; depends on hepatic blood flow (for flow-limited drugs like propofol, propofol CL ~1.5–2 L/min (very high — entire hepatic blood flow) fentanyl) or hepatic enzyme capacity (capacity-limited) Half-life t½ = 0.693 × Vd / CL; the time for plasma concentration to halve; for drugs Terminal t½ is often misleading for clinical practice — a drug with large (t½) with large Vd or low CL → long t½ Vd has long t½ even with high CL because drug continues to return from peripheral compartments; CSHT is more clinically relevant Context- The time for plasma concentration to fall 50% after stopping an infusion of a The most clinically relevant parameter for infusions: remifentanil CSHT = Sensitive specific duration ("context" = infusion duration); accounts for redistribution from 3 min (flat — no accumulation, organ-independent ester hydrolysis); Half-Time peripheral compartments back into plasma after stopping; CSHT INCREASES propofol CSHT rises slowly (short cases ~5 min; 8 hr case ~40 min — (CSHT) with longer infusion duration as peripheral compartments become still manageable); thiopentone CSHT rises steeply (very long — not progressively saturated suitable for infusion)

Drug Vd CL t½β CSHT Protein Binding Key Clinical Feature

Propofol Large: 200– Very high: Biphasic: α- Short and 98% protein Rapid induction AND relatively predictable recovery from 500 L (3- 1.5–2 L/min phase 2–4 only bound (albumin); infusions; suitable for TIVA; cardiorespiratory depression compartment) (exceeds min moderately reduced in dose-dependent; pain on injection (use large vein, lidocaine hepatic blood (redistribution, increasing: 5 hypoalbuminaemia pre-treatment) flow — responsible min after 1- → enhanced extrahepatic for clinical hr infusion; effect metabolism: recovery); β- ~40 min lung, kidney) phase 1–3 after 8-hr hours infusion

Thiopentone Large: ~400 Low: 0.15– Very long: 8– Rises very 80% protein Rapid induction from redistribution; single induction dose = L 0.25 L/min 12 hours (but steeply — bound brief action because drug redistributes to fat/muscle; repeat clinical offset becomes doses = accumulation in peripheral compartments → is from clinical prolonged recovery; still used for RSI and ICP reduction redistribution hangover (burst-suppression) not with elimination) repeated doses or infusion; NOT suitable for maintenance

Ketamine Large: 3 L/kg Moderate: 1 2–3 hours Moderate — 27% protein Dissociative anaesthesia; NMDA antagonist; preserves (highly lipid L/min suitable for bound airway reflexes and spontaneous ventilation; soluble) (hepatic N- bolus or sympathomimetic (raises BP/HR — useful in demethylation short haemodynamically compromised patients); bronchodilator; to infusion; increases ICP and IOP (controversial — may be used with norketamine norketamine sedation in ventilated patients); emergence delirium — active (active (benzodiazepine premedication reduces incidence) metabolite) metabolite) prolongs clinical effects

Etomidate Moderate: 4 High: 1 L/min 2–5 hours Moderate — 77% protein Most cardiovascularly stable induction agent — minimal L/kg (hepatic ester suitable for bound effect on MAP, HR, cardiac output; drug of choice for hydrolysis to induction; haemodynamically compromised patients (septic shock, inactive acid) not used for cardiogenic shock, cardiac tamponade) and for cardiac maintenance surgery induction; adrenal suppression (inhibits 11βhydroxylase → reduces cortisol and aldosterone synthesis for up to 12 hours after single dose — controversial, avoid in septic shock where adrenal function already stressed); myoclonus and pain on injection; increases seizure threshold (used in ECT)

Central compartment (V1 — blood + highly perfused organs) ↔ Peripheral compartment 1 (V2 — muscle — rapid equilibration) ↔ Peripheral compartment 2 (V3 — fat — slow equilibration)

After IV induction: drug rapidly enters the brain (part of V1 — high blood flow) → onset of effect; drug simultaneously redistributes to V2 (muscle) → plasma concentration falls → drug leaves the brain along the new gradient → patient wakes up; this redistribution-mediated recovery is why even thiopentone (long t½) produces short induction duration from a single bolus

With prolonged infusion: V2 and V3 progressively fill with drug; when the infusion stops, drug continues to return from V2 and V3 back to plasma → slows the fall in plasma concentration → CSHT rises with infusion duration; the extent of this depends on the lipid solubility and Vd of V3 (fat compartment) — drugs with very high fat solubility (thiopentone) have steeply rising CSHT; drugs with moderate fat solubility (propofol) have slowly rising CSHT

Nerve stimulation: a peripheral nerve (ulnar nerve at the wrist — most common; facial, posterior tibial as alternatives) is stimulated with surface or needle electrodes delivering supramaximal current pulses (20–60 mA for 0.1–0.2 ms; calibrated to exceed the maximum that produces maximum twitch — ensures all motor units are activated)

Response measurement: the mechanical or electrical response of the innervated muscle is measured; at the adductor pollicis (ulnar nerve → thumb adduction); quantitative devices measure the force or acceleration of thumb movement with each stimulus

Principle: residual NMB reduces the amplitude or number of twitches in proportion to the degree of receptor occupancy; the specific pattern of response varies by stimulation pattern and type of block (depolarising vs non-depolarising)

Pattern Description What It Detects Clinical Application Single Single supramaximal stimulus at 0.1 Hz (every 10 sec); Overall degree of block vs baseline; T1 = 0% Basic monitoring; requires a baseline preTwitch compares height to baseline (pre-NMB) twitch height; T1 = complete block; T1 = 25% → adequate NMB measurement; less used than TOF in expressed as % of baseline intubating conditions with most NMBs practice Train-of- Four supramaximal stimuli at 2 Hz (0.5 sec intervals) TOF count: 0 = profound block; 1 = deep The primary monitoring tool; no baseline Four (TOF) every 10–15 seconds; counts responses (TOF count = 0, block; 2–3 = moderate block; 4 = recovering; needed (counts 0–4 twitches); TOFR is the 1, 2, 3, or 4); measures ratio T4/T1 = TOFR TOFR: ratio of 4th to 1st twitch; TOFR <0.9 = criterion for safe extubation; fade pattern clinically significant residual block; TOFR (T4<T1) is pathognomonic for NON≥0.9 = adequate recovery depolarising block; no fade in depolarising (Phase I) block Double Two short bursts of 3 stimuli each at 50 Hz, separated by Detects residual block at TOFR 0.6–0.9 Useful for tactile/visual assessment when Burst 750 ms; easier to detect fade visually than TOF because better than TOF tactile assessment; fade in quantitative monitors unavailable; better Stimulation two larger responses are compared rather than four DBS (second response weaker than first) sensitivity than TOF for detecting residual (DBS) smaller ones indicates residual block block near extubation Tetanic Sustained high-frequency stimulation (usually 50 Hz for 5 Fade to tetanus indicates non-depolarising Confirms non-depolarising block character; Stimulation seconds); produces sustained muscle contraction block; sustained tetanus indicates either no used before PTC assessment (tetanus (50 or 100 (tetanus); in the presence of NON-depolarising block: block or Phase I depolarising block; NOT mobilises ACh stores for post-tetanic Hz) tetanic stimulation is not sustained → FADE of the tetanic routinely used (painful in awake patients); potentiation) contraction; in DEPOLARISING block (Phase I): no fade used in research Post- A 50 Hz tetanic stimulus for 5 seconds → 3-second Used when TOF count = 0 (no response to Guides decision between routine reversal Tetanic pause → single twitches at 1 Hz counted; the tetanic TOF); PTC 1–2 = deep block (→ (TOF≥2 → sugammadex 2 mg/kg) and deep Count stimulation temporarily mobilises ACh → post-tetanic sugammadex 4 mg/kg for reversal; reversal (PTC 1–2 → sugammadex 4 (PTC) potentiation → some twitches visible that were not neostigmine inadequate); PTC 0 = profound mg/kg) present before tetany; count the number of single block; PTC >10 = recovery imminent (TOF twitches detectable count about to reappear)

Feature Qualitative (Tactile/Visual) Quantitative (Acceleromyography — TOF-Watch) Method Anaesthesiologist feels or sees the response to TOF stimulation; Accelerometer attached to the thumb; piezoelectric transducer measures estimates fade by comparing T4 to T1 feel acceleration of thumb adduction; outputs TOFR as a number (0–1.0) TOFR threshold Fade detected only when TOFR <0.4 (60% of receptor occupancy); Provides exact TOFR; can detect TOFR 0.7, 0.8, 0.9 — the clinically for detection at TOFR 0.4–0.9 — "feels normal" to the clinician despite clinically dangerous range that qualitative monitoring misses completely dangerous residual block Clinical Patients extubated with TOFR 0.4–0.9 → postoperative residual Confirms TOFR ≥0.9 before extubation → eliminates PORC; Grosseconsequence of curarisation (PORC) → impaired airway protection, aspiration, Sundrup Lancet 2012: sugammadex + quantitative monitoring → significantly limitation hypoventilation, PTSD reduced pulmonary complications Evidence-based Insufficient for routine practice ASRA/AHA consensus 2018: quantitative monitoring should be the standard recommendation of care whenever NMBs are used; endorsed by major anaesthesia societies globally

Temperature effect: cool fingers → reduced acceleromyography signal → falsely low apparent block may be underestimated; ensure hand and monitoring site are warm; consider TOF at the corrugator supercilii (facial nerve) — less temperature-sensitive and more relevant for the diaphragm/airway muscles than adductor pollicis (which is more resistant to NMB than facial muscles)

Neuromuscular junction variability: different muscles have different sensitivities; adductor pollicis is MORE RESISTANT to NMB than the diaphragm and genioglossus; paradox: if TOF is measured at the thumb and TOFR = 0.7, the critical airway muscles (genioglossus, pharynx) may have TOFR = 0.4–0.5 → inadequate for safe extubation; this is why the TOFR threshold for extubation must be ≥0.9 at the adductor pollicis to ensure airway muscles are adequately recovered

8 glucose units in a ring (gamma-cyclodextrin); hydrophobic core encapsulates the steroidal nucleus of rocuronium or vecuronium → 1:1 high-affinity inclusion complex (Kd ~10⁻²⁵ mol/L); free plasma rocuronium concentration falls → rocuronium dissociates from NMJ receptors → NMJ function restored; no receptor activity — purely pharmacokinetic mechanism; inactive complex excreted renally

Clinical Situation NMJ Monitor Dose Expected Recovery Routine reversal (moderate block) TOF count ≥2 2 mg/kg actual body weight TOFR ≥0.9 within ~3 min Deep block reversal PTC 1–2 (TOF count = 0) 4 mg/kg actual body weight TOFR ≥0.9 within ~3 min

CICO emergency — immediate Within 3 min of rocuronium 1.2 mg/kg RSI 16 mg/kg actual body weight (push Spontaneous ventilation restored in ~2– reversal dose dose) 3 min

Issue Management Renal failure (eGFR <30) Complex excreted renally; accumulation with renal failure may cause delayed re-paralysis; use with caution; extended monitoring ≥24 hours; dialysis removes complex Oral contraceptives Progesterone may bind cyclodextrin cavity → reduced contraceptive efficacy equivalent to missing one OCP dose; advise additional barrier (OCP) contraception for 7 days post-administration Toremifene (breast High cyclodextrin affinity → displaces rocuronium → delayed/incomplete reversal; avoid sugammadex; use neostigmine or alternative NMB cancer treatment) Re-paralysis after 16 Sugammadex still present for hours; subsequent rocuronium/vecuronium doses will be unpredictably bound; if NMB needed within 24 hours mg/kg dose → use cisatracurium (not encapsulated by sugammadex)