POSTOPERATIVE VISUAL LOSS

👀 Corneal abrasion is the most common ocular complication after general anesthesia

👀 Ischemic Optic neuropathy (ION) and Central Retinal Artery Occlusion (CRAO) are the commonest causes for postoperative visual loss

👀 ISCHEMIC OPTIC NEUROPATHY (ION)

🌵More common among the two

🌵Most often seen after prolonged surgery in prone position 

🌵Venous congestion--> Raised Intra Ocular Pressure (IOP) due to Raised Intra Orbital Pressure --> Intra Orbital ‘Compartment Syndrome’

🌵Hypotension, Diabetes, Vascular disease, Smoking etc also may be important in the etiopathogenesis

🌵Treatment:

➖ Reduce optic nerve edema as it passes through posterior scleral foramen with steroids and mannitol 

➖ Optimal oxygen delivery by ensuring normal blood pressure and hematocrit  

➖ Clear all obstruction to venous drainage 

🌵Chance of visual recovery is less

👀 CENTRAL RETINAL ARTERY OCCLUSION (CRAO)

🌵 External pressure on eye and embolism are risk factors 

🌵 An echocardiogram and carotid ultrasound may help us to find an embolic source

Reference: White E, David DB. Care of the eye during anaesthesia and intensive care. Anaesth Intens Care Med. 2007; 8(9): 383–386.

Visual Analogue Scale & Statistical Concerns

🔸A frequently used tool in anaesthesia research is the 100 mm visual analogue scale (VAS). 

🔸This is most commonly used to measure postoperative pain, but can also be used to measure a diverse range of (mostly) subjective experiences such as preoperative anxiety, postoperative nausea, and patient satisfaction after ICU discharge. 

🔸Because there are infinite possible values that can occur throughout the range 0-100 mm, describing a continuum of pain intensity, most researchers treat the resulting data as continuous. 

🔸If there is some doubt about the sample distribution, then the data should be considered ordinal.

🔸When small numbers of observations are being analysed (say, less than 30 observations), it is preferable to consider VAS data as ordinal. 

🔸For a number of practical reasons, a VAS is sometimes converted to a 'verbal rating scale', whereby the subject is asked to rate an endpoint on a scale of 0-10 (or 0-5), most commonly recorded as whole numbers. In this situation it is preferable to treat the observations as ordinal data.

🔸There has been some controversy in the literature regarding which statistical tests should be used when analysing VAS data. 

🔸Mantha et al surveyed the anaesthetic literature and found that approximately 50% used parametric tests. 

🔸Dexter and Chestnuts used a multiple resampling (of VAS data) method to demonstrate that parametric tests had the greater power to detect differences among groups. 

🔸Myles et al have recently shown that the VAS has properties consistent with a linear scale, and thus VAS scores can be treated as ratio data. This supports the notion that a change in the VAS score represents a relative change in the magnitude of pain sensation. This enhances its clinical application.

Reference: Statistical Methods for Anaesthesia and Intensive Care, Paul S Myles and Tony Gin

A FEW PROSPECTIVE TECHNIQUES TO MEASURE ANALGESIA INTRA-OPERATIVELY

🤖Current electroencephalogram (EEG)-derived measures like BIS, provide information on cortical activity and hypnosis but are less accurate regarding subcortical activity, which is expected to vary with the degree of antinociception. 

🤖Efforts to develop methods for monitoring these subcortical activities produced a few indices, which may provide some use intra-operatively 

🤖Recently, the neurophysiologically based EEG measures of cortical input (CI) and cortical state (CS) have been shown to be prospective indicators of analgesia/anti-nociception and hypnosis, respectively. Composite Cortical State (CCS) is an alternate measure of CS.

🤖Composite Variability Index (CVI) is another recently developed EEG-derived measure of antinociception  based on a weighted combination of BIS and estimated electromyographic activity.

🤖CCS and BIS show strong correlations, suggesting that they behave similarly as indicators of hypnosis.

Reference: Comparisons of Electroencephalographically Derived Measures of Hypnosis and Antinociception in Response to Standardized Stimuli During Target-Controlled 

Propofol-Remifentanil Anesthesia, Mehrnaz Shoushtarian, Marko M. Sahinovic, Anthony R. Absalom, Alain F. Kalmar, Hugo E. M. Vereecke, David T. J. Liley and Michel M. R. F. Struys, anesthesia-analgesia, February 2016 • Volume 122 • Number 2

PIN INDEX AND COLOUR CODING

CAUSES OF DETERIORATION OF #GCS IN #NEUROSURGICAL #ICU

☑️IN A PATIENT WITH ANEURYSMAL-SAH, AFTER CLIPPING OR COILING 

❓Re-bleed 

❓Acute hydrocephalus 

❓Cerebral vasospasm 

❓Seizure

☑️ IN A PATIENT WITH TRAUMATIC BRAIN INJURY (#TBI)

❓Re-accumulation of haematoma 

❓ Haemorrhage into contusion 

❓ Oedema 

❓ Seizure

☑️IN A PATIENT, WHO UNDERWENT #CRANIOTOMY

❓ Haematoma (sub-dural/intracerebral etc.) 

❓ Oedema 

❓ Seizure 

❓ Pneumocephalus/ Air Encephalocoele

#NeuroAnesthesia , #NeuroCriticalCare , #NeuroIntensiveCare , #NeuroICU , #Anaesthesiology , #Anesthesiologist , #Anesthesia , #CriticalCare

VASOACTIVE AGENTS; DO YOU KNOW ?

Evidence suggests that dopamine can produce mild cerebral vasodilatation.

Phenylephrine can be the drug of choice when the cardiac index (CI) is sufficient but MAP is below the goal

Dobutamine does not have any dopaminergic agonist action.

In case of Labetalol, a reduction in MAP usually occurs when the dose is sufficient to decrease HR

propanolol shifts the hemoglobin-oxygen dissociation curve to the right.

Milrinone can induce thrombocytopenia as well as hypotension.

SNP is associated with the activation of the renin-angiotensin system ; reflex tachycardia can interfere with blood pressure reduction.

Occasionally, patients demonstrate relative resistance to SNP and they are at particular risk for developing cyanide toxicity.

SNP causes more arteriolar than venular vasodilatation, while NTG causes more venular than arteriolar vasodilatation.

Vasopressin increases arterial tone ; it is administered as a constant infusion, and not titrated up to avoid severe complications of distal ischemia.

Reference: Newfield, Philippa; Cottrell, James E., Handbook of Neuroanesthesia, 4th Edition

THE SUCCESS OF KETAMINE IN REFRACTORY SEIZURES, WHERE BENZODIAZEPINES FAIL

🔴In status epilepticus is there is a reduction in expression of “benzodiazepine-sensitive” GABAA-R d2 subunits 

🔴Also there is a 20-fold loss of potency in benzodiazepine receptors after 30 minutes.

🔴But there is an increase in the expression of excitatory NMDA receptors occurs, leading to seizure propogation

🔴Continued seizures result in BBB dysfunction facilitating leakage of albumin into the CNS, with a resultant proconvulsant effect by stimulating astrocytes to release NMDA and causing cerebral vasoconstriction.

🔴With continuing seizures, inhibitory GABA receptors are internalized in clathrin-coated vesicles, and excitatory NMDA receptors are mobilized to the membrane. This receptor trafficking may result in decreased inhibitory control and increased excitation that may foster status epilepticus. 

🔴The strong NMDA antagonist effect of ketamine has anticonvulsant effects and has the potential to prevent glutamate-mediated neurotoxicity. 

🔴Williams et al used a dose of 5 mg/kg/h in patients to control the seizures. The literature shows that doses as high as 7.5 mg/kg/h used for up to 14 days were safe.

🔴"With ketamine use, a concern about increasing intracranial pressure has been raised in ventilated patients. However, ketamine may not significantly elevate intracranial pressure and may provide some degree of neuroprotection by inhibiting the NMDA-receptor activation and interfere with the inflammatory response to injury when used in typical sedative or anesthetic doses."

🔴Ketamine may be the ideal agent for the control of seizure in patients with refractory seizures and septic shock in the intraoperative setting.

REFERENCE:

Use of Ketamine for Control of Refractory Seizures During the Intraoperative Period ; Williams, George W. MD; Cheng, Yuen C. MD; Sharma, Aanchal MD, Journal of Neurosurgical Anesthesiology, October 2014, Volume 26, Number 4

THE SECOND COMING OF METHOXYFLURANE

Ⓜ️Initially developed as an inhalational anesthetic, but withdrawn due to concerns about nephrotoxicity and hepatotoxicity. 

Ⓜ️In view of its analgesic properties it is now used, mainly in Australia and New Zealand, to provide short-term analgesia for painful procedures and in the prehospital setting (Grindlay and Babl, 2009). 

Ⓜ️Administration is via a dedicated single-use inhaler dispensing 0.2–0.4% methoxyflurane. 

Ⓜ️The limited data on efficacy suggest that methoxyflurane administered as a single dose as described above provides effective analgesia resulting in high patient satisfaction with no evidence of toxicity (Grindlay and Babl, 2009). 

Ⓜ️There is no good evidence regarding the safety of repeated doses, for example, for analgesia during daily dressing changes.

Ref: 

Acute Pain Management; A Practical Guide, Pamela E. Macintyre , Stephan A. Schug, 4/e

Systemic complications of aneurysmal subarachnoid hemorrhage

🔺Hypovolemia

🔺Hyponatremia

🔺Hypokalemia

🔺Hypocalcemia

🔺Electrocardiographic abnormalities

🔺Pulmonary edema

🔺Pneumonia

🔺Pulmonary embolus

🔺Hepatic dysfunction

🔺Renal dysfunction

🔺Thrombocytopenia

🔺Gastrointestinal bleeding

SURGICAL APPROACHES FOR VARIOUS ANEURYSMS

🌀FRONTO TEMPORAL (PTERIONAL ) CRANIOTOMY 

🔺Allows access to most aneurysms on lateral and anterior Circle of Willis vessels.

🔺Internal Carotid : Paraclinoid / Superior hypophyseal artery

🔺Internal Carotid : Ophthalmic artery

🔺Posterior Commununicating Artery

🔺Anterior Choroidal artery

🔺Internal Carotid Bifurcation 

🔺Middle Cerebral Artery

🔺Anterior Commununicating Artery

🌀PTERIONAL / SUBTEMPORAL APPROACH 

🔺Upper Basilar Artery

🔺Superior Cerebellar Artery

🌀SUBOCCIPITAL APPROACH 

🔺Vertebral Artery

🔺Posterior Inferior Cerebellar Artery

🌀COMBINED SUBTEMPORAL AND SUBOCCIPITAL APPROACH 

🔺Basilar trunk

🔺Vertebrobasilar Junction

NSAIDS-COMPARISON

ANTI INFLAMMATORY PROPERTIES 

〰〰〰〰〰〰〰〰〰〰〰〰〰

✨BETTER THAN NAPROXEN :

🔹Flurbiprofen

🔹Indomethacin

✨GOOD:

🔹Naproxen

🔹Fenoprofen

🔹Ketoprofen

🔹Tiaprofenic acid

🔹Diclofenac

🔹Aceclofenac

🔹Etodolac

🔹Nabumetone

🔹Piroxicam

🔹Tenoxicam

🔹Etoricoxib

✨WEAK:

🔹Ibuprofen

🔹Mefenamic acid

SIDE EFFECTS 

〰〰〰〰〰

✨FEWER SIDE EFFECTS 

🔹 Ibuprofen 

✨GREATER THAN IBUPROFEN

🔹 Naproxen

🔹 Fenoprofen(GI)

🔹 Flurbiprofen(GI)

🔹 Ketoprofen

🔹 Diclofenac

🔹 Aceclofenac

🔹 Sulindac

🔹 Tenoxicam

✨HIGH

🔹 Indomethacin

🔹 Piroxicam 

✨HIGH RISK OF RASH

🔹 Fenbufen

✨SEVERE CYSTITIS

🔹 Tiaprofenic Acid

✨DIARRHOEA & HEMOLYTIC ANEMIA

🔹 Mefenamic acid

✨LOW G.I.; BUT HIGH C.V. EFFECTS

🔹 Celecoxib

🔹 Etoricoxib

Reference: 

Medicines Optimisation Academy 

British National Formulary

PAIN IN GUILLAIN BARRE SYNDROME

✔️GBS a number of different subtypes

✔️The most common is an acute inflammatory demyelinating polyradiculoneuropathy 

✔️More than half of patients report severe pain. 

✔️Severe widespread neuropathic pain may be described, often without the features of a peripheral neuropathy, as well as musculoskeletal pain. 

✔️May sometimes have severe acute pain, 

✔️Treatment with systemic ketamine and/or lidocaine as well as gabapentin/pregabalin and carbamazepine may be of benefit in the acute phase (ANZCA and FPM, 2010).

Ref: Acute Pain Management: A practical guide,4/e, Pamela E. Macintyre , Stephan A. Schug

Nonthrombolytic therapy for patients who are not candidates for rTPA after ischemic stroke

TARGET: 

✔️optimization of CBF

✔️prevention of secondary brain injury, infarct extension & hemorrhagic conversion 

✔️avoid post-stroke complications (e.g., pulmonary embolus and aspiration pneumonia)

✔️ early mobilization and rehabilitation

✔️ attention to psychiatric ( e.g. Depression) and social consequences of stroke and assistance with daily activities.

(1) Airway management, hemodynamic monitoring, and treatment of increased ICP 

(2) aggressive antihypertensive therapy may exacerbate ischemia by decreasing CBF. A generally accepted cutoff for the administration of antihypertensive therapies is SBP >220 mm Hg, DBP >120 mm Hg, or MAP >130 mm Hg. 

(3) In the absence of hemorrhage on a CT scan, antiplatelet therapy is initiated in the form of aspirin starting with 325 mg by mouth followed by 81 to 160 mg daily.

(4) Multiple studies have failed to show a benefit to heparin administration ; but anticoagulation is usually initiated when atrial fibrillation is present.

(5) Hyperglycemia worsens neurologic outcome. So , euglycemia (80 to 110 mg/dL) is beneficial if it can be achieved without substantially increasing the risk of hypoglycemia.

(6) Seizures are treated with phenytoin, loading dose 15 mg/kg i.v. over 20 minutes followed by 5 to 7 mg/kg/day, or fosphenytoin, loading dose PE 15 to 20 mg/kg i.v., and then 4 to 6 PE mg/kg/day.

(7) DVT prophylaxis is provided using pneumatic compression or low-molecular-weight heparin e.g. enoxaparin, 0.5 mg/kg subcutaneously twice a day.

(8) After the evaluation of airway reflexes and adequacy of swallowing, nutrition is provided via a suitable route.

(9) A few studies suggest that positioning the head end of the bed at 15° for patients who have normal ICP improves CBF and neurologic function.

(10) Rehabilitation and psychiatric evaluation. e.g. Treatment of depression and other psychiatric comorbidities facilitates rehabilitation and improves functional status.

Ref: Seth Manoach, Jean G. Charchaflieh, Handbook of Neuroanesthesia, 4th Edition, Lippincott Williams & Wilkins

ANAESTHETIC IMPLICATIONS IN EPILEPSY SURGERIES

✔️If Awake Craniotomy/ wake up testing is planned, the procedure details should be explained to the patient, including what he/she is expected to hear and feel, inside the O.R.

✔️Get a brief description of the seizures and any prodromal symptoms 

✔️Continue anti epileptics through the morning of surgery

✔️Antiepileptics can reduce duration of action of NMBAs

✔️Usually a preoperative WADA test or fMRI would have been done, to check, whether the side of proposed surgery has any cerebral dominance or speech function 

✔️Abnormal LFTs can be expected with long term Valproate or Carbamazepine therapy

✔️WHAT THE COMMON AEDs DO?

✔️Phenytoin and Phenobarbitone: Reduce Hematocrit

Carbamazepine, Valproate,Ethosuximide and Primidone : Reduce platelet count

Carbamazepine and Primidone: Reduce WBC count

✔️If a difficult intubation is anticipated ( for e.g. After fixation of stereotactic frame ), an awake fibreoptic intubation can be considered 

✔️Moderate Sedation, if required can be achieved with Propofol 25-75 ug/kg/min plus Remifentanil 0.02-0.05 ug/kg/min OR Dexmedetomidine 1ug/kg/min over 10 minutes followed by 0.2-0.7 ug/kg/min

✔️Anticipated Surgical duration: 3 hours

✔️EBL: 250-500 ml ; blood transfusions are seldom needed

✔️Pain score 2-4

✔️If an Asleep-Awake-Asleep technique is used:

GA  continued for positioning, craniotomy and till the exposure of the surgical area. Then patient is allowed to awaken, to monitor neurological function during brain stimulation ( LMA removed OR  if ETT, it is removed over a tube exchanger). When seizure area, is fully delineated, GA is reinstituted.

ADVERSE EFFECTS OF UNDER TREATED SEVERE ACUTE PAIN

(Reference: Pamela E. Macintyre,Stephan A. Schug. ACUTE PAIN MANAGEMENT; A PRACTICAL GUIDE)

👹Tachycardia, hypertension

👹increased myocardial oxygen consumption, myocardial ischemia

👹 Decreased lung volumes, atelectasis, decreased cough, sputum retention, infection, hypoxemia

👹Decreased gastric and bowel motility 

👹Urinary retention 

👹Increased catabolic hormones: glucagon, growth hormone, vasopressin, aldosterone, renin, and angiotensin 

👹Reduced anabolic hormones: insulin, testosterone 

👹Catabolism leads to hyperglycemia, increased protein breakdown and negative nitrogen balance; ➡️impaired wound healing and muscle wasting 

👹 Muscle spasm, immobility (increasing risk of deep-vein thrombosis-->pulmonary embolism) and muscle wasting 

👹 Chronic (persistent) pain due to central sensitization 

👹 Anxiety, fear, helplessness, sleep deprivation—leading to increased pain and potential long-term psychological effects

TRAMADOL AND ONDANSETRON: THEY ARE NOT A GOOD PAIR ! ; WHY FORCING THEM TO LIVE TOGETHER ?

Tramadol- highlights 

➖➖➖➖➖➖➖➖

✔️both opioid and non-opioid modes of action. . 

(1) inhibition of noradrenaline re-uptake 

(2)increased release and decreased re-uptake of serotonin in the spinal cord, and 

(3)a weak effect on mu opioid receptors

✔️The weak, opioid effect is mediated by an active metabolite, (+)-M1 (O-desmethyltramadol), formed via the genetically polymorphic P450 CYP2D6 iso-enzyme system. The biological activity of this system is variable, and individuals may be classified as extensive or poor metabolisers of tramadol. 

✔️Tramadol’s affinity for opioid receptors is about 6000 times weaker than morphine, but the (+)-M1 metabolite has an affinity about 200 times greater than tramadol. Poulsen et al. report much higher concentrations of the (+)-M1 metabolite and greater analgesic efficacy of tramadol in extensive metabolisers compared to poor metabolisers. Also noted was a reduction of nausea, vomiting and tiredness amongst poor metabolisers

Ondansetron-highlights

➖➖➖➖➖➖➖➖➖

✔️Ondansetron competitively antagonises serotonin, subtype 3 (5-HT3) receptors in the CTZ and enteric neurones. 

✔️ Peripheral 5-HT3 receptors are also involved in nociceptive pathways and ondansetron may alter 5-HT3 nociceptive responses at the level of dorsal horn neurones

✔️ Ondansetron can block sodium channels in a similar fashion to local anaesthetic agents, and exhibit agonist activity at mu opioid receptors, thus resulting in a peripheral anti-nociceptive effect.

Tramadol + Ondansetron 

➖➖➖➖➖➖➖➖➖

✔️PONV due to Tramadol is often managed with a competitive serotonin antagonist, ondansetron

✔️ There is evidence that the concurrent use of these two drugs results in a mutual reduction of effect—tramadol is a less potent analgesic and ondansetron is a less effective as an antiemetic. 

✔️ But the effect of ondansetron on tramadol consumption diminished with time. 

✔️ De Witte et al. found a significant (50%) increase in cumulative tramadol consumption during the first post-operative hour when patients were given ondansetron along with Tramadol.

✔️ Ondansetron is, in part, metabolised by the CYP2D6 iso-enzyme system—an iso-enzyme system responsible for formation of an active tramadol metabolite that has analgesic effect . Competition for this metabolic pathway may result in a reduction in formation of the (+)-M1 metabolite of tramadol and a consequent reduction in analgesic efficacy.

DO YOU KNOW❓😳 additional points➕

✔️ There is animal and human evidence that both tramadol and ondansetron have local anaesthetic type properties.

✔️ Ondansetron was approximately fifteen times more potent than lignocaine and may well be a prototype molecule for the development of a new group of local anaesthetic agents. 

✔️ These findings are further supported in a human clinical study by Memis et al.which showed that tramadol and ondansetron both significantly reduced the pain associated with the injection of the neuromuscular blocking drug, rocuronium.

(Ref: J.H. Ye, W.C. Mui, J. Ren, T.E. Hunt, W.H. Wu, V.K. Zbuzek Ondansetron exhibits the properties of a local anesthetic. Anesth. Analg., 85 (1997), pp. 1116–1121)

✔️Tropisetron and granisetron are able to reverse an acetaminophen-mediated analgesia completely.

 

〰〰〰〰〰〰〰〰〰〰〰〰〰〰〰〰〰〰〰〰〰

References:

Anaesthesia. 2015 Feb;70(2):209-18. doi: 10.1111/anae.12948. Epub 2014 Dec 10.

The effect of ondansetron on the efficacy of postoperative tramadol: a systematic review and meta-analysis of a drug interaction.

Stevens AJ1, Woodman RJ, Owen H.

Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-HT3 Spinal Receptor Involvement in Acute Pain in Humans

Arcioni, Roberto MD*,; della Rocca, Marco MD*,; Romanò, Sarah MD*,; Romano, Rocco MD†,; Pietropaoli, Paolo MD*, and; Gasparetto, Alessandro MD*

ScienceDirect Review

Aspects of tramadol and ondansetron interactions Bruce Hammonds, David A. Sidebotham, Brian J. Anderson,

📝BRAIN TUMOURS-SYMPTOMATOLOGY

📌Contralateral signs :  are associated with lesions in the posterior frontal area (motor) or anterior parietal lobe (sensory)

📌Lesions in the dominant hemisphere: Aphasia

📌Lesions in the non dominant hemisphere: Apraxia

📌Temporal lobe lesions : Focal seizures with auras and visual field defects

📌Frontal lobe lesions : Altered cognitive functioning and subtle personality changes

📌Subfrontal lesions : Anosmia

📌Sellar and Parasellar lesions: Visual field and Acuity problems , hypopituitarism, oversecretion syndromes (Cushing Syndrome, Acromegaly)

📌Tumours in relation to Ventricular system : Hydrocephalus , Raised ICP

📌Tumours of the brainstem and cerebellopontine angle : Cranial nerve palsies , long tract signs , secondary hydrocephalus

📌Lesions of Cerebellar vermis : Truncal ataxia

📌Lesions in Cerebellar hemisphere: Appendicular signs such as incoordination and nystagmus 

Reference:

Page :617-618, Bailey and Love’s , SHORT PRACTICE OF SURGERY , 24 th edition

BASICS: POTENCY, DURATION AND ONSET OF ACTION OF LOCAL ANESTHETICS⚙

🗡POTENCY: 

👉🏿is affected by several factors including:

🔹Hydrogen ion balance

🔹Fiber size, type, and myelination

🔹Vasodilator/vasoconstrictor properties (affects rate of vascular uptake)

🔹Frequency of nerve stimulation

🔹pH (acidic environment will antagonize the block)

🔹Electrolyte concentrations (hypokalemia and hypercalcemia antagonizes blockade)

↔️Duration of action 

🔹is associated with lipid solubility. 

🔹Highly lipid soluble local anesthetics have a longer duration of action due to decreased clearance by localized blood flow and increased protein binding.

⏱ONSET OF ACTION

🔹Local anesthetics are weak bases and contain a higher ratio of ionized medication compared to non- ionized. 

🔹Increasing the concentration of non-ionized local anesthetic will speed onset. 

🔹In general, local anesthetics with a pKa that approximates physiologic pH have a higher concentration of non- ionized base resulting in a faster onset. 

🔹On the other hand, a local anesthetic with a pKa that is different from physiologic pH will have more ionized medication which slows onset. 

🔹For example, the pKa for lidocaine is 7.8 and 8.1 for bupivacaine. Lidocaine is closer to physiologic pH than bupivacaine. Lidocaine has a greater concentration on non-ionized local anesthetic than bupivacaine which results in a faster onset. 

🔹 Non-ionized and ionized portions of local anesthetic solution exert distinct actions. 

🔹 Lipid soluble, non-ionized form of the local anesthetic penetrates the neural sheath and membrane. 

🔹 In the cell, the non-ionized and ionized forms equilibrate. 

🔹 The ionized form of the local anesthetic binds with the sodium channel. Once “bound” to the sodium channel, impulses are not propagated along the nerve.

🔹 Clinically, onset of action is not the same for all local anesthetics with the same pKa. This is due to the intrinsic ability of the local anesthetic to diffuse through connective tissue. 

🔹 Local anesthetics with a pKa closest to the physiological pH generally have a higher concentration of non-ionized molecules and a more rapid onset. 

🔹 Two notable exceptions are chloroprocaine and benzocaine. Chloroprocaine has a high pKa and rapid onset. Benzocaine does not exist in an ionized form and exerts its effects by alternate mechanisms.

➖➖➖➖➖➖➖➖➖➖➖➖➖➖➖➖➖➖➖➖

#LocalAnesthetics, #RegionalAnesthesia , #Pharmacology , #anaesthesia

References

Heavner, J.E. (2008). Pharmacology of local anesthetics. In D.E. Longnecker et al (eds) Anesthesiology. 

Joyce, J.A. (2002). A pathway toward safer anesthesia: stereochemical advances. AANA Journal, 70, 63-67.

Katzung, B.G. (1992). Section 1: basic principles. In B.G. Katzung Basic & clinical pharmacology, 5th edition. Norwalk, Connecticut: Appleton and Lange.

Morgan, G.E., Mikhail, M.S., Murray, M.J. (2006). Local Anesthetics. In G.E. Morgan et al Clinical Anesthesiology, 4th edition. 

Stoelting, R.K. & Hillier, S.C. (2006). Pharmacology and pharmacodynamics of injected and inhaled drugs. In R.K. Stoelting & S.C. Hillier (eds) Pharmacology & Physiology in Anesthetic Practice, 4th edition. 

Strichartz, G.R. & Berde, C.B. (2005). Local Anesthetics. In R.D. Miller Miller’s Anesthesia, 6th edition

ANESTHESIA INFO FROM THE LAY MEDICAL MAN- Facebook Page

XENON-THE STRANGER🌪

🍭colorless, odourless, tasteless gas

🍭four times denser than air. 

🍭density and viscosity are substantially higher than those of other inhalational anaesthetics. 

🍭occurs in extremely low concentrations (0.0875 ppm) in the atmosphere, hence its name from the Greek ‘xenos’ meaning ‘stranger’. 

🍭Xenon has been used experimentally as an anaesthetic for more than 50 years 

🍭Recently there has been a renewed interest in xenon as a safe, effective and more environmentally friendly substitute for nitrous oxide (Sanders et al. 2003). 

🍭manufactured by fractional distillation of liquefied air, currently at a cost of US $10 per litre (i.e. about 2,000 times the cost of producing N2O). This high cost is the major factor limiting its more widespread use, even when used in low-flow delivery systems. 

🍭Xenon has many of the properties of an ideal anaesthetic. 

🍭Its blood/gas partition coefficient (0.12) is lower than that of any other anaesthetic, giving rapid induction and emergence. 

🍭It is unlikely to be involved in any biochemical events in the body, and is not metabolised. 

🍭Xenon causes no significant changes in myocardial contractility, blood pressure or systemic vascular resistance, even in the presence of severe cardiac disease (Sanders et al. 2005). 

🍭The unique combination of analgesia, hypnosis, and lack of haemodynamic depression in one agent would make xenon a very attractive choice for patients with limited cardiovascular reserve 

🍭In contrast to other inhaled anaesthetic agents, xenon slows the respiratory rate and increases the tidal volume, thereby maintaining minute ventilation constant. 

🍭Airway pressure is increased during xenon anaesthesia, due to its higher density and viscosity rather than direct changes in airway resistance (Baumert et al 2002). 

🍭Because of its high cost xenon must be used in low-flow closed circuits. Crucial to this method of administration is accurate measurement of the concentration of xenon in the circuit. This measurement is generally difficult as xenon is  diamagnetic and does not absorb infrared radiation (commonly used to measure the  concentrations of other agents), and its low reactivity precludes the use of specific fuel cell or electrode-type devices. 

🍭Xenon conducts heat better than other gases, and a technique based on thermal conductivity has proved to be effective (Luginbuhl et al 2002). 

🍭Because xenon is heavier than air, the speed of sound is slower in xenon than that in air, and this difference has been also been used to measure xenon concentration. 

🍭Because xenon is a normal constituent of the atmosphere, it does not add to atmospheric pollution when emitted from the anaesthesia circuit. This is in contrast to the other inhalational anaesthetics, which have ozone-depleting potential and pollute the atmosphere when released from the anaesthesia system (Marx et al. 2001). 

🍭On a molecular basis, N2O is 230 times more potent as a greenhouse gas than carbon dioxide. N2O released as a waste anaesthetic contributes roughly 0.1% of total global warming. The lifetime of N2O in the atmosphere is long—approximately 120 years. 

🍭The anaesthetic actions of xenon are thought to result primarily from noncompetitive inhibition of  NMDA receptors (De Sousa et al. 2000), a property it shares with nitrous oxide. 

🍭In common with other NMDA receptor antagonists, xenon appears to have neuroprotective properties (Sanders et al. 2003). 

🍭Xenon is also an excellent analgesic, an action mediated by NMDA receptors (De Sousa et al. 2000). 

🍭Xenon also inhibits the plasma membrane Ca 2+   pump, altering neuronal excitability and inhibiting the nociceptive responsiveness of spinal dorsal horn neurones. 

(Reference : Jürgen Schüttler •  Helmut Schwilden Modern Anesthetics ,Handbook of Experimental Pharmacology, vol 182)