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The PRONE Equation: Precision Pain‑Breaking Approach

Multimodal, pre‑emptive and balanced analgesia are central to ERAS pathways, aiming to reduce the surgical stress response, minimize opioids, facilitate early mobilization and prevent breakthrough pain. The PRONE framework (Paracetamol, Regional anesthesia, Opioids, NSAIDs and “Extra” agents) provides a practical way to structure intraoperative and postoperative analgesia within these principles.

# # Concept of multimodal, pre‑emptive and balanced analgesia

Multimodal analgesia combines drugs and techniques with different mechanisms of action to achieve superior pain control with fewer side effects than any single agent alone. Pre‑emptive analgesia targets nociceptive pathways before the surgical stimulus, reducing central sensitization and subsequent pain intensity. Balanced analgesia mirrors “balanced anesthesia”: appropriate contributions from systemic agents, regional techniques and non‑pharmacological measures to avoid both under‑ and over‑treatment. ERAS guidelines emphasize opioid‑sparing multimodal regimens and early transition to oral medications to support gut function and mobilization.

# # P – Paracetamol

Paracetamol should be given as a foundation analgesic, ideally before incision (oral/IV) and then regularly postoperatively rather than on an “as needed” basis. It acts centrally and has a strong opioid‑sparing effect, improving quality of analgesia and reducing nausea, sedation and ileus associated with opioids. Within ERAS, scheduled paracetamol is almost universal, with dose adjustments in low body weight or hepatic impairment.

# # R – Regional anesthesia

Regional techniques are the cornerstone of opioid‑sparing multimodal analgesia and strongly supported by ERAS. Options include neuraxial (epidural, spinal with intrathecal morphine for select procedures), peripheral nerve and plexus blocks (e.g. TAP, ESP, femoral/adductor canal, interscalene, infraclavicular), and wound/infiltration catheters. When instituted pre‑incision, regional blocks contribute to pre‑emptive analgesia by blocking afferent input and limiting central sensitization, and continuous techniques give stable background analgesia that helps prevent breakthrough pain.

# # O – Opioids

Opioids remain important rescue and background agents but should no longer be the sole or dominant strategy. Intraoperatively, short‑acting opioids (e.g. fentanyl, remifentanil) are titrated to hemodynamic response, while regional and non‑opioid agents carry the main analgesic load. Postoperatively, ERAS recommends oral opioids in the lowest effective dose, preferably PRN on top of a strong non‑opioid base rather than long‑acting parenteral infusions. Patient‑controlled analgesia (PCA) can be used where regional is not possible, but the goal is to step down quickly to oral regimens as gut function returns.

# # N – NSAIDs

NSAIDs and COX‑2 inhibitors provide powerful anti‑inflammatory and opioid‑sparing effects, and their routine use (where not contraindicated) is a key ERAS element. Pre‑ or intraoperative dosing plus regular postoperative administration reduces pain scores and opioid consumption and therefore decreases nausea, ileus and respiratory depression. Caution is needed in patients with renal impairment, heart failure, bleeding risk or gastrointestinal disease, and dose and duration should be individualized.

# # E – Extra (others)

The “Extra” component includes several adjuvants that enhance multimodal, pre‑emptive and balanced analgesia. Low‑dose ketamine attenuates central sensitization and is particularly useful in major surgery and opioid‑tolerant patients. Intravenous lidocaine infusions during abdominal surgery may reduce pain, ileus and hospital stay, fitting well with ERAS goals. Gabapentinoids can reduce early opioid needs but must be balanced against sedation and dizziness, especially in older patients. Alpha‑2 agonists (clonidine, dexmedetomidine) add analgesia and sympatholysis, though hemodynamic and sedative effects must be monitored. Non‑pharmacological measures—good positioning, splinting, ice/heat, early physiotherapy and psychological preparation—further support pain control.

# # Preventing breakthrough pain within ERAS

Preventing breakthrough pain requires planned, scheduled baseline therapy plus timely rescue rather than reactive dosing. Pre‑incision loading of paracetamol, NSAID and regional block, followed by continuous or regular dosing postoperatively, maintains analgesic plasma levels and block effect. Clear escalation plans (e.g. stepwise increases in regional infusion rates or oral opioid rescue) and frequent pain assessment allow early intervention before severe pain recurs. By systematically applying the PRONE framework within ERAS, perioperative teams can deliver robust multimodal, pre‑emptive and balanced analgesia, minimizing opioid burden and avoiding breakthrough pain while supporting rapid, safe recovery.

Which coagulation factors are not synthesised by liver hepatocyte?

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🔑 Potassium and Insulin in DKA

• In DKA, total body potassium is always depleted due to osmotic diuresis, vomiting, and secondary hyperaldosteronism.
• However, serum potassium may appear normal or even high initially because acidosis and insulin deficiency drive potassium out of cells.
• Insulin therapy shifts potassium back into cells, which can cause a dangerous drop in serum potassium if it is already low.

📌 Guideline Recommendations

• If serum K⁺ < 3.3 mmol/L → Do NOT start insulin.
⁠◦ First, give IV potassium replacement until K⁺ is > 3.3 mmol/L.
• If serum K⁺ 3.3–5.2 mmol/L → Start insulin with concurrent potassium supplementation (usually 20–30 mmol KCl per liter of IV fluid).
• If serum K⁺ > 5.2 mmol/L → Start insulin, but monitor potassium closely and replace as soon as it falls into the normal range.

⚠️ Why this matters

• Starting insulin when K⁺ < 3.3 mmol/L can precipitate life-threatening arrhythmias, respiratory muscle weakness, or cardiac arrest.
• That’s why potassium correction takes priority over insulin in this scenario.

Question of the day

◉ Extrinsic pathway
This is the fastest pathway, triggered when blood is exposed to tissue factor (Factor III)from outside the blood vessel due to injury. Tissue factor and Factor VIIa form a complex that activates Factor X, initiating the common pathway.

➔ PT assessment: The PT test works by adding a reagent called thromboplastin (which contains tissue factor and phospholipids) to a patient's plasma sample. This immediately activates the extrinsic pathway. The time it takes for the plasma to clot primarily reflects the function of Factor VII.

◉ Intrinsic pathway
This pathway is slower and is triggered when blood comes into contact with a negatively charged surface, such as exposed collagen in an injured blood vessel. It involves Factors XII, XI, IX, and VIII.

➔ aPTT assessment: The aPTT test is designed to measure this pathway. An activating agent (like silica or kaolin) and phospholipids are added to the patient's plasma to start the intrinsic pathway. This allows the measurement of the time to clotting for all the intrinsic factors.

◉ Common pathway
This is the final stage where both the extrinsic and intrinsic pathways converge to form a stable clot. It begins with the activation of Factor X (Xa) and involves Factors V, II (prothrombin), and I (fibrinogen).

➔ Both PT and aPTT assessment: Since the common pathway is the final sequence of clotting regardless of the initial trigger, both tests are affected by deficiencies in the common pathway factors. If there is an issue with Factor V, Factor II, or Fibrinogen, both the PT and aPTT will be prolonged. The difference between the two tests lies in whether a problem is found in the intrinsic or extrinsic factors before the common pathway begins.

🧨Wearable Cardioverter-Defibrillator (WCD)

• A WCD is an external device (like a vest) worn by patients for a limited time when they are at risk of life-threatening ventricular arrhythmias, but either are not candidates yet for an implantable defibrillator, or are in a “bridge period” (following a myocardial infarction, or while waiting for recovery or implantation).
• It monitors the heart rhythm and delivers shocks if dangerous arrhythmias (ventricular tachycardia or fibrillation) occur. The patient is alerted and can abort an inappropriate shock if conscious.

◉ Implications for anaesthetic practice
From what is known about similar devices (implantable defibrillators, subcutaneous ICDs, etc.), some probable recommendations and important considerations are:
• Preop planning: Identify that patient has a WCD; check its settings; ensure it’s functioning and charged; understand how it responds to interference, whether the wearer can disable alarms or shocks if needed.
• Electromagnetic interference (EMI): Electrocautery (especially monopolar), diathermy, other surgical instruments can generate EMI, which might trigger inappropriate detection or shocks from the WCD. Might need to minimize use, or use bipolar instruments, or use short bursts, put the return pad far from the device, etc.
• Backup safety: Even if the WCD is in place, one must have external defibrillator/pads ready, because the WCD might be removed, fail, or be temporarily disabled.
• Intraoperative handling: The WCD garment might interfere with surgical field access or sterile draping; it may need to be adjusted. Also, the device’s electrodes might interfere with other monitoring leads.
• Postop care: After surgery, ensure the WCD is resumed if disabled; check for any shocks or arrhythmias during surgery; re-evaluate its function.

Current guidelines relevant to postoperative delirium (POD)

➔ ASA 2025 Practice Advisory (older adults, inpatient surgery).
● Screen frailty and cognition; manage modifiable risks; educate family.
● No superiority of neuraxial vs general anesthesia for delirium reduction; TIVA vs volatile also neutral—choose by patient/surgical needs.
● Consider dexmedetomidine (balance bradycardia/ hypotension).
● Emphasize multimodal analgesia, normothermia, early mobilization (ERAS).

➔ ESAIC 2024/2025 update on postoperative delirium (adult)
● Early risk screening, non-pharmacologic bundles (sleep, orientation, mobilization), minimize deliriogenic drugs, multimodal analgesia, treat precipitating factors. Extended, updated European recommendations (2024; update notice 2025).

➔ SCCM PADIS (ICU) — 2018 guideline with 2025 focused update.
● Implement ICU Liberation A-F bundle (pain control, light sedation, delirium monitoring with tools like CAM-ICU, early mobility, sleep hygiene).
● Avoid deep/long benzodiazepine sedation; use non-pharmacologic measures first; antipsychotics only when severe agitation threatens safety. 2025 update refines recommendations but maintains core bundle approach.

Why Blood Transfusion is Avoided in Cancer Surgery

◉ Transfusion-related immunomodulation (TRIM)
o Allogeneic blood transfusion can cause suppression of cell-mediated immunity.
o Leads to decreased natural killer (NK) cell activity, reduced T-cell function, and altered cytokine balance.
o This immunosuppression can favour tumour cell survival and proliferation.

◉ Risk of tumour recurrence and metastasis
o Studies have shown an association between peri-operative blood transfusion and increased risk of cancer recurrence and reduced overall survival in colorectal, gastric, hepatocellular, and other malignancies.
o Mechanism: circulating tumour cells during surgery + immunosuppression → easier implantation and spread.

◉ Increased infection risk
o Immunosuppression also predisposes to surgical site infection, pneumonia, and sepsis.
o Infections may delay adjuvant chemotherapy/radiotherapy.

◉ Pro-inflammatory and pro-angiogenic effects
o Stored blood products release cytokines, growth factors, and bioactive lipids.
o These may promote angiogenesis and tumour growth.

◉ Transfusion-related complications
o TRALI, TACO, febrile reactions, alloimmunisation, iron overload (with repeated transfusion).
o These increase perioperative morbidity and prolong hospital stay.

◉ Effect on survival
o Multiple meta-analyses report that peri-operative blood transfusion correlates with worse long-term survival in many cancers (though some confounding factors exist, anaemia itself, surgical complexity).

🎱 Practical Perioperative Strategy

➥ Restrictive transfusion thresholds are recommended (Hb < 7 g/dL in stable patients; < 8 g/dL if cardiovascular risk).

➥ Optimise preoperative haemoglobin with iron therapy, erythropoiesis-stimulating agents (if appropriate), correction of nutritional deficiencies.

➥ Use blood conservation methods: meticulous haemostasis, cell salvage (except in cases with contamination risk), acute normovolaemic haemodilution.

“Peri-operative allogeneic blood transfusion in cancer surgery is avoided because of transfusion-related immunomodulation, increased risk of tumour recurrence, infections, and poor survival outcomes; hence, a restrictive transfusion strategy with blood conservation is recommended.”

MAC in hypothyroidism and hyperthyroidism

● Hypothyroidism

MAC Value: Unchanged. The partial pressure of the anaesthetic gas required at the brain to prevent movement in response to a surgical stimulus is not directly affected by the level of thyroid hormone.

Clinical Reality: Patients with hypothyroidism are clinically very sensitive to the effects of all anaesthetic agents, including volatile anaesthetics. They will appear to require less anaesthetic.

Explanation: The sensitivity is not due to a change in brain requirement (MAC) but rather due to changes in drug delivery and systemic effects (pharmacokinetics).

→ Reduced Cardiac Output: A lower cardiac output means that the anaesthetic gas taken up from the lungs is delivered more slowly to the rest of the body's tissues. This causes the partial pressure in the blood and brain to rise more quickly toward the inspired concentration, leading to a faster induction of anaesthesia.
→ Altered Systemic Effects: Hypothyroid patients often have blunted baroreceptor reflexes and are prone to significant hypotension and bradycardia with anaesthetic agents.
→ Associated Hypothermia: Severe hypothyroidism can be associated with hypothermia. Hypothermia itself is a potent cause of decreased MAC. So, if a hypothyroid patient is cold, they will require less anaesthetic, but the cause is the low temperature, not the thyroid state directly.

🛑 Clinical Approach: You do not change your target MAC on the vaporizer based on thyroid status. However, you must be extremely cautious, titrate the agent very slowly, and be prepared to manage significant haemodynamic instability.

● Hyperthyroidism

MAC Value: Unchanged. Similar to hypothyroidism, the intrinsic requirement of the brain for the anaesthetic is not altered by excess thyroid hormone.

Clinical Reality: Anaesthetising a patient with untreated or poorly controlled hyperthyroidism can be very challenging. They have a hypermetabolic, hyperdynamic state.

Explanation:

→ Increased Cardiac Output: A high cardiac output means anaesthetic gas is rapidly taken up from the lungs and distributed throughout the body. This can slow the rate of rise of the partial pressure in the brain, potentially leading to a slower induction of anaesthesia.
→ Hyperdynamic State: The main challenge is managing the tachycardia, hypertension, and risk of arrhythmias caused by the high sympathetic tone. The focus is on controlling this sympathetic output with beta-blockers and ensuring adequate anaesthetic depth to blunt surgical stimulation, not on simply increasing the MAC value.
→ Associated Hyperthermia: Hyperthyroidism can cause a mild increase in core body temperature. Hyperthermia is a cause of increased MAC. If the patient is hyperthermic, they will require more anaesthetic, but again, this is due to the temperature change itself.

🛑 Clinical Approach: The primary goal is to ensure the patient is euthyroid (in a normal thyroid state) before any elective surgery. If emergency surgery is required, the focus is on aggressively managing the hemodynamic effects with beta-blockers and ensuring deep anesthesia to prevent a catastrophic thyroid storm, rather than focusing on a specific MAC value.