VASOPRESSIN AND DESMOPRESSIN: MECHANISM, DOSES AND SIDE EFFECTS

✔️Their binding to V1 receptors causes vasopressor effects. 

✔️Activation of V2 receptors in the collecting tubule increases water absorption 

✔️In the acute intensive care unit setting, aqueous vasopressin may be preferred due to its short duration of effect (2–8 hours) compared with that of desmopressin (6–18 hours) as DI may be a transient clinical situation.

✔️Vasopressin can be given subcutaneously in doses of 4–10 units every 6 hours as needed for urine output exceeding 200 mL.

✔️Alternatively, a continuous infusion can be used, as the half-life of vasopressin given IV is only 20 minutes. A dose of 0.008 – 0.04 units/kg/hour is usually effective

✔️If serum osmolality falls too low, the infusion can be stopped until osmolality is restored to the normal range. 

✔️DDAVP is a synthetic form of vasopressin that has less potent (2000- to 3000-fold) vasopressor effects than vasopressin. 

✔️It has a much longer duration of effect and is the preferred therapy for permanent or slowly resolving DI.

✔️It is available as intranasal, oral, or IV forms. 

✔️The intranasal preparation of DDAVP delivers a 10 ug dose per spray, and doses of 10-30 g per day are usually effective. 

✔️The IV form (4 ug/mL) is given IV, intramuscularly (IM), or subcutaneously in doses of 0.5–2  ug every 8–12 hours as needed. 

✔️Oral tablets (0.1–0.2 mg) in doses of 0.1–1.2 mg/day can also be given to obtain adequate diuresis.

✔️Cardiovascular effects such as acute myocardial ischemia, arrhythmias, and hypertension have been reported. 

✔️Peripheral vasoconstriction may cause cutaneous gangrene. 

✔️Thrombosis is a very rare complication of vasopressin and DDAVP, which occurs as a result of increasing levels of factor VIII and von Willebrand factor.

Reference: Considerations in Fluids and Electrolytes After Traumatic Brain Injury; Denise H. Rhoney and Dennis Parker, Jr Nutr Clin Pract 2006 21: 462

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