ننګرهارحوزوی روغتون،انستیزی څانګه.NRH.Anesthesia Department

17/09/2022

Pediaa.Com

Difference Between Isotonic Hypotonic and Hypertonic

Madhusha

5 years ago

Main Difference – Isotonic vs Hypotonic vs Hypertonic

A solution is a homogeneous liquid mixture of two or more components. A solution is made by dissolving a solute in a solvent. There are three types of solutions grouped based on their concentrations. The concentration of a solution is the amount of solute present in a unit volume of the solution. The concentration of a solution determines its osmotic pressure; the minimum pressure required to avoid a solution flowing through a semipermeable membrane. The main difference between isotonic hypotonic and hypertonic solutions is that isotonic solutions are solutions having equal osmotic pressures and hypotonic solutions are solutions having a lower osmotic pressure whereas hypertonic solutions are solutions with a high osmotic pressure.

Key Areas Covered

1. What is Isotonic
– Definition, Effect on Cells
2. What is Hypotonic
– Definition, Effect on Cells
3. What is Hypertonic
– Definition, Effect on Cells, Uses
4. What is the Difference Between Isotonic Hypotonic and Hypertonic
– Comparison of Key Differences
Key Terms: Concentration, Hypertonic, Hypotonic, Isotonic, Osmotic Pressure, Solutions, Turgidity

What is Isotonic

Isotonic solutions are solutions having equal osmotic pressures. This is due to the equal concentrations of solutes they have. Isotonic solutions have the same amount of solutes per unit volume of solution and the same amount of water.
When two isotonic solutions are separated from a semipermeable membrane, there is no net movement of solutes across the membrane since there is no concentration gradient between the two solutions. The rates of the movement of water from one solution to the other are equal. Therefore, the cells remain in their normal state. The shape of the cell is not changed; no swelling or shrinking occurs.

Figure 1: Isotonic

Osmotic pressure is the pressure required to be applied in order to avoid this solute movement through the semipermeable membrane. Isotonic solutions have equal osmotic pressures since the rates of movement of molecules through the semipermeable membrane are equal.
Some examples for solutions that are isotonic with animal cells are given below.

Saline (0.98%)

Dextrose in water (5%)

What is Hypotonic

A hypotonic solution is a solution having a lower osmotic pressure. The low osmotic pressure is a result of low solute concentration. Osmotic pressure is the pressure required to be applied in order to avoid this solute movement through the semipermeable membrane. When a hypotonic solution is separated from another solution via a semipermeable membrane, the solute movement through the membrane is less. Therefore the pressure that needs to be applied in order to stop this movement is also less.
When a cell is exposed to a hypotonic environment, the amount of water inside the cell is less than that of the hypotonic solution. This is because, in hypotonic solutions, a less amount of solutes are dissolved in a high amount of water. Then the cell swells. The internal pressure of the cell is increased and the cells may even burst.

Figure 2: Hypotonic

Hypotonic solutions can cause turgidity in plant cells. When water enters the plant cell, the cell swells up. As a result, the cell membrane is pushed towards the plant cell wall. The cell wall can avoid the cell bursting. This process is turgidity, or we call this swelled cell a “turgid cell”.

What is Hypertonic

A hypertonic solution is a solution having a higher osmotic pressure when compared to other solutions. Since hypertonic solutions have higher solute concentrations, a very high pressure has to be applied in order to avoid this solution from flowing through a semipermeable membrane.
When a hypertonic solution and another solution (that is not hypertonic) are separated from a semipermeable membrane, the solutes of the hypertonic solution tends to move across the semipermeable membrane. This is because the hypertonic solution has a higher solute concentration and the solutes can move along a concentration gradient (from a high concentration to a low concentration). A semipermeable membrane is a biological or synthetic membrane that allows some molecules and ions to pass through it.

Figure 3: Hypertonic

Osmotic pressure is the pressure required to be applied in order to avoid this solute movement through the semipermeable membrane. Since the concentration of a hypertonic solution is very high, the pressure required to avoid the solute movement is also high. Hence the osmotic pressure is high.
Hypertonic solutions are used to preserve food. For example, when some fruits or fish is dipped in a hypertonic salt or packaged with a hypertonic solution, it can kill microbes in the environment inside the package. This is because microbial cells have a high amount of water than solutes and the amount of water in a hypertonic solution is very low. Therefore water flows out of the cells according to the concentration gradient. The lack of water causes the shrinking of the cell and eventually kills microbes.

Figure 1: Turgidity in Plant Cells



Difference Between Isotonic Hypotonic and Hypertonic

Definition

Isotonic: Isotonic solutions are solutions having equal osmotic pressures.
Hypotonic: Hypotonic solutions are solutions having lower osmotic pressures.
Hypertonic: Hypertonic solutions are solutions having comparatively higher osmotic pressures.

Solute Concentration

Isotonic: Isotonic solutions have equal solute concentrations.
Hypotonic: Hypotonic solutions have a low concentration.
Hypertonic: Hypertonic solutions have a high concentration.

Effect on Cells

Isotonic: Isotonic environments show no effect on cells.
Hypotonic: Hypotonic environments cause cells to swell.
Hypertonic: Hypertonic environments cause cells to shrink.

Food Preservation

Isotonic: Isotonic solutions are not helpful in food preservation.
Hypotonic: Hypotonic solutions are not helpful in food preservation.
Hypertonic: Hypertonic solutions are helpful in food preservation since they kill microbes in the food package.

Conclusion

Tonicity is the relative concentration of solutes dissolved in a solution which determines the direction and extent of the movement of molecules across a semipermeable membrane. There are three types of solutions based on the tonicity; isotonic solutions, hypertonic solutions and hypotonic solutions. The main difference between isotonic hypotonic and hypertonic solutions is that isotonic solutions are solutions having equal osmotic pressures while hypotonic solutions are solutions having a lower osmotic pressure and hypertonic solutions are solutions with a high osmotic pressure.

References:

1. Helmenstine, Ph.D. Anne Marie. “What Is Does Hypertonic Mean?” ThoughtCo, Available here.
2. Dewi Sivasamy Follow. “The effects of hypotonic, hypertonic and isotonic.” LinkedIn SlideShare, 26 Feb. 2013, Available here.
3. “Cells in Hypotonic Solutions.” Pearson – The Biology Place, Available here.

Image Courtesy:

1. “Blausen 0685 OsmoticFlow Isotonic” By Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. – Own work (CC BY 3.0) via Commons Wikimedia
2. “Blausen 0684 OsmoticFlow Hypotonic” By Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. – Own work (CC BY 3.0) via Commons Wikimedia
3. “Blausen 0683 OsmoticFlow Hypertonic” By Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. – Own work (CC BY 3.0) via Commons Wikimedia
4. “Turgor pressure on plant cells diagram” By LadyofHats (Public Domain) via Commons Wikimedia

Categ

16/08/2022

08/08/2022

Thyroid Storm

Thyroid storm, also known as thyrotoxic crisis, is an acute, life-threatening complication of hyperthyroidism that presents with multi-system involvement. It is an exaggerated presentation of thyrotoxicosis. Thyroid storm is a state of decompensation from thyrotoxicosis. It is an abrupt exacerbation of hyperthyroidism due to sudden excessive thyroid hormone release in the circulation.it usually occur 6-24 hrs after surgery but can occur intraoperatively. It is a medical emergency. Without treatment, mortality rates can reach 90%. It can be precipitated by physiologic or pharmacologic stresses.

Precipitating factors:
• Abrupt discontinuation or irregular use of antithyroid medicine
• Thyroid surgery
• Non-thyroid surgery
• Trauma
• Acute illness like infections, diabetic ketoacidosis, acute myocardial infarction, cardiovascular accident, cardiac failure, drug reaction
• Parturition: Labour and delivery
• Recent use of Iodinated contrast medium
• Radioiodine therapy (rare)
• Burns
• Stroke: Cerebrovascular accident
• Medication side effect e.g. amiodarone, anesthetics, salicylates.
• Anaesthetic stress
• Large amounts of iodine

Pathophysiology:
• The pathophysiological basis for precipitation of thyroid storm in patients with thyrotoxicosis is not clear. But, a precipitating factor, as mentioned above, is always required to cause thyroid storm.
• Several hypotheses have been purposed.
• One hypothesis suggests the incidence of thyroid storm is due to the rapid increase in thyroid hormone levels, rather than the absolute hormone level that occurs during thyroid surgery, following radioactive iodine treatment, after sudden discontinuation of the antithyroid drug, or after administration of the large dose of iodine in contrast studies.
o The hyperactivity of the sympathetic nervous system with increased response to catecholamine along with an increased cellular response to thyroid hormone during acute stress or infections, causing cytokines release and altered immunological disturbances, are other possible mechanisms of thyroid storm.
o The clinical features are due to the exaggerated effects of the thyroid hormone.
o There is intense metabolic activity which increases oxygen requirements. The resulting tachycardia to meet the oxygen requirements can induce heart failure and predisposes the patient to arrhythmias.
o Similarly, the CNS symptoms include irritability, seizures, delirium, and eventually coma.

Symptoms and sign:
• Hyperpyrexia to 104 to 106°F is common.
• Cardiovascular symptoms:
o Tachycardia to rates that can exceed 140 beats/minute
o Congestive heart failure
o Hypotension
o Cardiac arrhythmia: Atrial fibrillation
o Death from cardiovascular collapse
• Central nervous system dysfunction:
o Agitation,
o Anxiety
o Delirium
o Psychosis
o Altered mentation
o Confusion
o Stupor
o Coma
• Other symptoms: may include
o Severe nausea
o Vomiting
o Diarrhoea
o Sweating
o Dehydration and shock
o Hyperventilation
o Abdominal pain
o Hepatic failure with jaundice
o Fluid losses from perspiration, nausea, vomiting, and diarrhea predispose to hypovolemic hypotension. Heart failure can also produce hypotension.
o The accompanying fever could result in hypovolemia, tachycardia, congestive heart failure, shock, and coma.

History and Physical exam:
• Presentation of thyroid storm is an exaggerated manifestation of hyperthyroidism, with the presence of an acute precipitating factor.
• Fever, cardiovascular involvement (including tachycardia, heart failure, arrhythmia), central nervous system (CNS) manifestations, and gastrointestinal symptoms are common.
o Fever of 104 F to 106 F with diaphoresis is a key presenting feature.
o Cardiovascular manifestations include tachycardia more than 140 HR/minute, heart failure with pulmonary edema and peripheral edema, hypotension, arrhythmia, and death from cardiac arrest.
o CNS involvement includes agitation, delirium, anxiety, psychosis, or coma. Gastrointestinal (GI) symptoms include nausea, vomiting, diarrhea, abdominal pain, intestinal obstruction, and acute hepatic failure.
• Physical examination findings may include:
o High temperature
o Tachycardia
o Orbitopathy
o Lid lag
o Goiter
o Hand tremors
o Moist and warm skin
o Hyperreflexia
o Systolic hypertension
o Jaundice.

Evaluation:
• The diagnosis of thyroid storm needs clinical suspicion based on the presentation mentioned above in a patient with hyperthyroidism or suspected hyperthyroidism.
• One should not wait for lab results before starting treatment. Thyroid function tests can be obtained which usually show high FT4/FT3 and low TSH. It is not necessary to have a very high level of thyroid hormone to cause thyroid storm.
• Other lab abnormalities may include hypercalcemia, hyperglycemia (due to inhibition of insulin release and increased glycogenolysis), abnormal LFTs, high or low white blood cell (WBC) count.
• Burch-Wartofsky Point Scale (BWPS): In 1993, the following scoring system for the diagnosis of thyroid storm was introduced:
o Temperature: 5 points per 1 F above 99 F (maximum 30 points)
o CNS dysfunction: 10 points for mild (agitation), 20 for moderate (delirium, psychosis or extreme lethargy), and 30 for severe (seizure or coma)
o Tachycardia: 5 (99-109), 10 (110 -119), 15 (120 -129), 20 (130 -139) and 25 (greater than 140)
o Presence of atrial fibrillation:10
o Heart failure: 5 for mild (pedal edema), 10 for moderate (bi-basilar rales), 15 for severe (pulmonary edema)
o GI dysfunction: 10 for moderate (diarrhea, nausea/vomiting or abdominal pain) and 20 for severe (unexplained jaundice)
o Presence of Precipitating factor: 10 points
Diagnosis: A total score of more than 45 is highly suggestive of thyroid storm, 25 to 44 supports the diagnosis, and less than 25 makes the diagnosis unlikely.
• The Japanese Thyroid Association (JTA): This is a different scoring system based on similar clinical findings. Thyrotoxicosis (elevated FT3 and/or FT4) is a prerequisite, and it requires various combinations of following symptoms:
o CNS manifestation (restlessness, delirium, psychosis/mental aberration, lethargy/somnolence, coma)
o Fever (38 C/100.4 F or greater)
o Tachycardia (130/min or higher)
o CHF (pulmonary edema, rales, cardiogenic shock, or NYHA class IV)
o GI/Hepatic Manifestation (Nausea, vomiting, diarrhea, total Bilirubin 3 mg/dl or more
• Diagnosis:
o Definite Thyroid Storm (TS1): Thyrotoxicosis (elevated FT3 and/or FT4) plus
 At least one CNS manifestation plus one or more other symptoms (fever, tachycardia, CHF, GI/Hepatic) ‘OR’ A combination of at least three features among fever, GI/Hepatic, CHF, or tachycardia
o Suspected Thyroid Storm (TS2): Thyrotoxicosis (elevated FT3 and/or FT4) plus
 A combination of at least two features among tachycardia, CHF, GI/Hepatic, Fever ‘OR’ A patient with h/o thyroid disease, presence of goiter and exophthalmos who meets criteria for TS1 but TFTs not available
• A chest x-ray may be done to assess heart failure.
• Head CT may help exclude a neurological cause in some patients.
• An ECG is often done to monitor for arrhythmias.

Laboratory findings:
• All patients with overt primary hyperthyroidism have low TSH and high free T4 and/or T3 concentrations.
• The degree of thyroid hormone excess typically is not more profound than that seen in patients with uncomplicated thyrotoxicosis.
• Other nonspecific laboratory findings may include mild hyperglycemia, mild hypercalcemia, abnormal liver function tests, leukocytosis, or leukopenia.
• Hyperglycemia is secondary to a catecholamine-induced inhibition of insulin release and increased glycogenolysis.
• Hypercalcemia may occur due to hemoconcentration and enhanced bone resorption.
• ECG: arrhythmias
• X-ray

Differential diagnosis:
• Malignant hyperthermia
• Neuroleptic malignant syndrome
• Sepsis
• Hemorrhage
• Pheochromocytoma
• Transfusion reaction

Treatment:
• Treatment includes rapid alleviation of thyrotoxicosis, fluid resuscitation, cooling measures to counter fever, medications to control heart rate, and glucocorticoids.
• Treatment of thyroid storm revolves around three principles:
1. Block thyroid hormone production and secretion.
2. Stop the conversion of T4 to T3.
3. Antagonize the b-adrenergic effects of thyroid hormones.

Specific strategic steps for treatment:
• A beta blocker to control the symptoms and signs induced by increased adrenergic tone
• A thionamide to block new hormone synthesis
• An iodine solution to block the release of thyroid hormone
• An iodinated radiocontrast agent (if available) to inhibit the peripheral conversion of T4 to T3
• Glucocorticoids to reduce T4-to-T3 conversion, promote vasomotor stability, possibly reduce the autoimmune process in Graves' disease, and possibly treat an associated relative adrenal insufficiency
• Bile acid sequestrants may also be of benefit in severe cases to decrease enterohepatic recycling of thyroid hormones

A. Pharmacological treatment:
• Block adrenergic-like effects:
o Drug used:
 Propranolol 1-2 mg IV every 10-15 min or 20-120 mg PO every 4-6 hours
 Esmolol 50-100 mg/kg/min
 Diltiazem 5-10 mg/hour IV or 60-120 mg PO every 6-8 hours
 Lignocaine : 1.0-1.5 mg/kg
 Digoxin is indicator in case of atrial fibrillation to control ventricular rate.
o After initial supportive measures, a beta-blocker should be started for any case of suspected thyroid storm.
 Typically, propranolol 40 mg to 80 mg is given every 4 to 6 hours.
 Propranolol is frequently selected for initial therapy because in high doses, it inhibits the type 1 deiodinase, which may help reduce serum T3 levels.
 The intravenous dose is 0.5 to 1 mg over 10 minutes followed by 1 to 2 mg over 10 minutes every few hours.
 As an alternative to intravenous administration, propranolol can be given orally or via nasogastric tube in a dose to achieve adequate control of heart rate, typically 60 to 80 mg orally every four to six hours.
o Esmolol, a short-acting beta-blocker, at a loading dose of 250 mcg/kg to 500 mcg/kg followed by 50 mcg/kg to -100 mcg/kg/minute can be given in ICU setting. This regimen permits rapid titration of the drug to achieve adequate beta blockade while minimizing adverse reactions.
o For patients with reactive airway disease, cardioselective beta-blockers like atenolol or metoprolol should be chosen. If there is a contraindication for the use of beta-blockers, diltiazem is an alternative.
• Block thyroid hormone production:
o A loading dose of propylthiouracil (PTU) 500 mg to 1000 mg followed by 250 mg every 4 hours or Methimazole (MMI) 20 mg every 4 to 6 hours should be given.
o Propylthiouracil is favored because it has a small but additional effect of blocking the peripheral conversion of T4 to T3.
o Doses:
 PTU 200-400 mg PO every 6-8 hours
 Methimazole 20-25 mg PO every 6 hours
• Block thyroid hormone release:
o One hour after the first dose of thionamide is taken, administer iodine (saturated solution of potassium iodide [SSKI], 5 drops orally every six hours or Lugol's solution, 10 drops every eight hours). The administration of iodine should be delayed for at least one hour after thionamide administration to prevent the iodine from being used as substrate for new hormone synthesis in patients with toxic adenoma or toxic multinodular goiter (since the etiology of the thyrotoxicosis is frequently uncertain at the time of admission).
o Drug used:
 Lugol solution 4-8 drops PO every 6-8 hours
 SSKI 5 drops PO every 6 hours
 Iopanoic acid 1 g PO every 8 hours for 1 day, then 500 mg PO every 12 hours
 Lithium carbonate 300 mg PO every 8 hours
o Iodinated radiocontrast agents:
 Iodine-containing solutions have traditionally been utilized for the treatment of thyroid storm since iodine blocks the release of T4 and T3 from the gland within hours.
 Iopanoic acid and other iodinated radiocontrast agents used for oral cholecystography have been used to treat hyperthyroidism.
 They are, however, potent inhibitors of T4-to-T3 conversion, and the release of iodine in pharmacologic quantities from these agents has the additional benefit of blocking thyroid hormone release. They have been extremely useful in treating severe hyperthyroidism and in preparing hyperthyroid patients for urgent surgery.
 If available, these agents can be given to patients with severe hyperthyroidism at a dose of 0.5 to 1 g once daily.
 Because they are iodinated, they should be given at least one hour after the thionamide to prevent the iodine from being used as substrate for new hormone synthesis.
• Block T4 to T3 conversion:
o Hydrocortisone 100 mg IV every 8 hours
o Glucocorticoids reduce T4-to-T3 conversion.
• Bile acid sequestrants:
o Thyroid hormones are metabolized in the liver, where they are conjugated with glucuronide and sulfate, and the conjugation products are excreted in the bile. Free thyroid hormones are released in the intestine and are reabsorbed.
o Bile acid sequestrants (eg, cholestyramine 4 g orally four times daily) have been found to reduce thyroid hormone levels in thyrotoxic patients by interfering with enterohepatic circulation and recycling of thyroid hormone.
o They are useful adjunctive therapy in patients with thyroid storm, particularly in patients who are intolerant of thionamides.
• If thionamide therapy is contraindicated because of an allergic reaction, thyroidectomy is needed after treatment with a beta-blocker, hydrocortisone, cholestyramine, and iodine solution.

B. Supportive therapy:
• Fluids
• Cooling: cold crystalloid fluid infusion or cooling mattress
• Re-hydration
• If circulatory shock is present, an intravenous direct vasopressor (phenylephrine) is indicated.
• Meperidine to inhibit shivering 12.5 mg IV every 10 min 3 2
• Acetaminophen 650 mg PO every 4-6 hours
• Broad spectrum antibiotics
• Plasmapheresis and exchange transfusion in severe cases.
• IPPV may require in respiratory failure.
• If any precipitating factors, for example, infection, are present, that needs to be taken care of.
• Patients with thyroid storm must be admitted to the intensive care unit with close cardiac monitoring and ventilatory support if needed.

C. Other therapies:
• Plasmapheresis:
o Plasmapheresis has been tried when traditional therapy has not been successful. Plasmapheresis is the last resort if all other measures fail.
o Plasmapheresis removes cytokines, antibodies, and thyroid hormones from plasma.
• Lithium: Lithium has also been given to acutely block the release of thyroid hormone. However, its renal and neurologic toxicity limit its utility.

D. Long-term management:
• After there is evidence of clinical improvement (defervescence, resolution of central nervous system and cardiovascular manifestations), iodine therapy can be discontinued and glucocorticoids tapered and discontinued.
• Beta blockers can be withdrawn but only after thyroid function tests have returned to normal.
• The dose of thionamides should be titrated to maintain euthyroidism.
• PTU, if given, should be switched to methimazole because of methimazole's better safety profile and better compliance rates.
• In patients with Graves' disease, definitive therapy with radioactive iodine or thyroidectomy is important to prevent a recurrence of severe thyrotoxicosis.
o Radioiodine therapy is first choice for definitive therapy for hyperthyroidism in the absence of moderate to severe orbitopathy, given its lower cost and lower complication rate compared with surgery.
o If the patient received iodine within a few weeks of planned radioiodine treatment, a radioiodine uptake should be obtained to calculate the radioiodine treatment dose rather than using fixed-dose radioiodine treatment.
o Surgery may be required in patients with grave's disease for the treatment of hyperthyroidism. These patients need to be pre-treated with beta-blockers, glucocorticoids, and iodine formulas. Surgery is usually done after 5-7 days.
(Ref: Morgan+Stoelting+uptodate.com+ ncbi.nlm.nih.gov/books)

08/08/2022

KETOFOL
Ketofol is the combination of ketamine and propofol in various concentrations.

It commonly used for several procedures.

A combination of these drugs provides sedation, analgesia, and rapid recovery with hemodynamic stability and minimal respiratory depression

Ketamine basics:
• Ketamine, a neuroleptic anesthetic agent, works on thalamocortical and limbic N-methyl-D-aspartate (NMDA) receptors.
• It can be given through intravenous or intramuscular routes.
• Ketamine gives a dissociative sedative, analgesic, and amnestic effect.
• It works by inhibiting catecholamine uptake, which exerts a sympathomimetic effect.
• Ketamine stimulates the cardiorespiratory system. A direct effect increases cardiac output, arterial blood pressure, heart rate and central venous pressures. Therefore, it is a valuable agent for hypotensive or hypovolemic patients, but a less desirable agent in patients with ischemic heart disease or raised pulmonary vascular pressure.
• However, ketamine induces psychomimetic activity and emergence reactions in up to 30% of patients.
• The typical dose is 1–2 mg/kg IV or 4–5 mg/kg IM. Additional doses may be required at increments of 0.5-1 mg/kg.

Propofol basics:
• Propofol is a sedative, hypnotic and anesthetic agent, is also an antagonist at N-methyl-D-aspartate receptors.
• Propofol is a lipophilic, ultra short-acting hypnotic agent, which works by potentiating GABA receptors on the neuronal lipid membranes.
• Propofol gives rapid sedation and antiemetic effects.
• It does not provide any analgesia, and therefore should not be used as a sole agent for sedation.
• Propofol has a narrow therapeutic range and risks of cardiovascular depression.
• Propofol-based sedation is safe and highly effective. Mild respiratory adverse events occur frequently and major complications may happen rarely. Additionally, the adverse events do not occur more frequently compared to other sedation regimens. As a result, the combination of these two drugs has several advantages.
• Note that one of its advantages is its anti-emetic property with a very low incidence of vomiting.
• Typical dosing is 1-2 mg/kg bolus followed by either a continuous infusion at 0.05-0.1 mg/kg/min or by 0.5 mg/kg boluses every 2 – 3 minutes.

Ketofol Basics:
• Ketamine is an anesthetic drug that is importantly analgesic without respiratory depression, increased blood pressure, and heart rate, whereas Propofol has good sedation and rapid recovery but causes respiratory depression, decreased blood pressure, and heart rate.
• A combination of these drugs provides sedation, analgesia, and rapid recovery with hemodynamic stability and minimal respiratory depression.
• Ketofol (ketamine and Propofol mixture) is a good combination of drugs for PSA in painful procedures in pediatrics resulting in hemodynamic and respiratory safety.
• Use of low ketamine in combination helps to have decreased recovery time and minimal side effects.

How to prepare Ketofol:
• There is no real standard dosing regimen established.
• The convenient 1:1 dilution (200 mg of each) simplifies the preparation of ketofol.
• Ketamine comes in a 50 mg/mL concentration, so if you take a 10 mL saline flush and empty 2 mL and draw up 2 mL of ketamine you have 100 mg of ketamine.
• Propofol comes in a standard 10 mg/mL concentration. So if you fill a 10 mL syringe with this you have 100 mg of propofol.
• If you mix the two in a new 20 or 30 mL syringe you get 100 mg ketamine + 100 mg propofol = 200 mg total. Now every one mL has 10 mg of ketofol.

Dose:
• The dosage of ketofol depends on the age and physical status of the patient.
• Your starting dose of this will be 0.5 mg/kg followed by another 0.5 mg/kg after about 30-60 sec. From then on for maintenance you can use 0.25 mg/kg as needed.
• In some cases, we used an initial bolus of 2 to 3 ml followed by an infusion of between 3 and 8 ml per hour, titrated to effect.
• However in some case, a larger bolus and infusion rate were used due to the patient’s large body mass.
• Some patients also required small doses of midazolam and fentanyl.

Advantage of Ketofol:
• Dose requirement of ketamine and propofol is less (0.5 mg/kg )
• Total sedation time is less (13 min).
• Recovery time is early
• Number of adverse events is less such as less vomiting
• Spontaneous ventilation of the patient. No patients required BVM ventilation or intubation.
• Satisfaction scores higher for patients/parents, nurses, and physicians.
• The adverse effects of ketamine and propofol are balanced by each other.
o Propofol also causes cardiorespiratory depression. However, the addition of ketamine should counteract this. Similarly, other characteristics of propofol and ketamine appear to be complementary.
o Propofol blunts the emetogenic and psycho-cognitive effects of ketamine and ketamine adds an analgesic effect not provided by propofol.

Indication:
• Diagnostic imaging requiring sedation only
o Paediatrics MRI
• Painful diagnostic procedures
o Lumber Puncture
o Sexual assault examination
• Painful therapeutic procedures
o Fracture/dislocation reduction
o Complex laceration repair
o Wound debridement
o Burn care
o Foreign body removal
o Abscess drainage
o Tube insertion
o Electrical cardioversion
o Menstrual regulation(MR)
o Dilation and curettage (D&C)

Contraindications:
• There are no absolute contraindications to procedural sedation and analgesia (PSA).
• Relative contraindications may include:
o Older age
o Significant medical comorbidities
o Signs of a difficult airway

Risk reduction:
• To reduce the risk of adverse events in older adults and patients with major comorbid disease, we suggest a more conservative approach to PSA medications, including:
o Giving a lower starting dose
o Using slower rates of administration
o Repeated dosing of medications at less frequent intervals
• Aspiration risk:
o Carefully consider the risks and benefits of performing the procedure immediately.
o It may be reasonable to wait if the patient's stomach is full and the procedure is not a true emergency.
o Avoid deep sedation.
o Consider using ketamine for sedation in cases where delay is not possible and the risk of aspiration is elevated, as ketamine maintains protective airway reflexes.
o Avoid the administration of preprocedural antacids or promotility medications. T
• Considerations in pregnancy:
o Pre-procedural administration of medication to improve gastroesophageal sphincter tone and reduce gastric volume (eg, metoclopramide) and decrease stomach acidity (eg, H2 antagonists, sodium citrate) may reduce the risk of vomiting and aspiration and is unlikely to cause harm.
o Pre-procedural hydration and left lateral displacement of the uterus (in the late second and the third trimester) helps to reduce the risk of hypotension, uteroplacental insufficiency, and resultant fetal hypoxemia.
o Oxygen by face-mask is administered because of the risk of sedation-related maternal desaturation (primarily due to decreased functional residual capacity).

Conclusion:
Ketofol is a combination of ketamine and propofol. It is an agent of choice for various procedures. The combination of propofol and ketamine has several benefits because of hemodynamic stability, lack of respiratory depression, good recovery and potent post-procedural analgesia. The safety and efficacy of ketofol as a sedoanalgesic agent are depended on the dose and the ratio of the mixture. Therefore, ketofol should be an ideal combination drug for procedural sedation.
(copied from Anaesthesia page.)