Hi, I am Beth Ann Clayton, and I'd like to welcome you to the Oxytocin Administration Lecture. The learning objective for this presentation is to discuss anesthetic considerations for cesarean delivery related to the administration of the first-line uterotonic oxytocin. I have no financial relationships with any commercial interests related to the content of this activity, and I will not discuss off-label use during my presentation. Endogenous oxytocin is a hormone that's produced in the hypothalamus and released into the bloodstream by the pituitary gland. It is a polypeptide chain containing nine amino acids. Oxytocin receptors exist throughout the body, primarily in the myometrium and the endometrium of the uterus. However, they also exist in the cardiovascular system and central nervous systems, and these are the locations we typically see the side effects arise from. In addition, there is substantial increase in oxytocin receptors in the uterus towards the end of pregnancy. Therefore, exogenous oxytocin may not be beneficial in the earlier trimesters, and you may need to utilize a different uterotonic in the first and second trimesters. Pitocin is the exogenous form of oxytocin. It's a synthetic preparation with rapid onset and a short half-life. It is utilized as the first-line therapy for prophylaxis of uterine atomy after the delivery of a third-trimester pregnancy. It works in two ways. First, the pitocin will cause direct contrial effect of the myometrium. In addition, pitocin also increases the production of prostaglandin PFG2-alpha in the endometrium, which also stimulates uterine contractions. Oxytocin is rapidly metabolized by hepatic oxytocinases and cleared in the urine and bile. Because of its rapid metabolism, its half-life is less than six minutes. Consequently, a prolonged infusion is more effective than a bolus administration in preventing uterine atomy. Exogenous oxytocin can be associated with serious side effects, including vasodilatation. Oxytocin has a direct relaxing effect on vascular smooth muscle, which leads to decreased systemic vascular resistance, hypotension, and tachycardia. A rapid IV bolus of oxytocin can cause hypotension due to this decrease in systemic vascular resistance and cardiac output, which can ultimately result in cardiovascular collapse if not treated. Tachycardia may also result due to the administration of oxytocin. This is from the direct effect on the specific oxytocin receptors in the myocardium of the heart, subsequently resulting in alterations in AV conduction and myocardial repolarization. Patients receiving exogenous oxytocin may also complain of chest pain because the oxytocin can induce coronary vasoconstriction. Lastly, water intoxication is a concern because oxytocin structure is similar to vasopressin and therefore has antidiuretic hormone-like activity. High doses of oxytocin administered along with large volumes of IV fluid, especially those containing free water, can lead to hyponatremia, seizures, and coma. These side effects described are related to the dose administered of oxytocin, its rate of administration, the presence of comorbidities in the barcherian, such as preeclampsia or cardiac disease. The overall volume status of the patient and repeated doses of oxytocin. It has been demonstrated that patients who receive a higher dose of oxytocin have a higher incidence of nausea and vomiting compared to patients who have a lower dose of oxytocin. As you can see, if a patient receives 2 international units of oxytocin, they have a 5% chance of nausea and vomiting compared to 33% if they receive 5 international units. Vomiting shows similar in that a patient receiving 2 international units of oxytocin has a 2.5% chance of vomiting, but it goes up to 15% with 5 international units of oxytocin. Therefore, it is advantageous to try to achieve the minimum administration amount of oxytocin that proves therapeutic. As mentioned, oxytocin administration can cause hypotension. Therefore, the administration of phenylephrine can mitigate adverse hemodynamic consequences. However, phenylephrine may not be necessary if you avoid the large bolus dose of oxytocin or if you maintain the oxytocin infusion rate below 1 international unit per minute. Postpartum oxytocin administration occurs in a wide range of doses, also delivery methods, whether it's bolus or infusion, and timing patterns before or after the delivery of the placenta. Research has demonstrated that small doses are sufficient to produce adequate uterine contractions after cesarean delivery. The dose of oxytocin required to generate satisfactory uterine tone after delivery is lower than previously thought. The ED90 of bolus dose oxytocin for satisfactory uterine tone within 3 minutes for cesarean delivery in non-laboring women is 0.35 international units. However, in women that are undergoing a cesarean delivery for labor arrest after either a labor augmentation or an induction with oxytocin, their ED90 is almost 10 times higher at approximately 3 international units. The ED90 for oxytocin administered via an infusion without a bolus dose is approximately 0.3 international units per minute in non-laboring women, but it does increase to approximately 0.71 international units in women exposed to oxytocin during labor before the cesarean delivery. Women receiving oxytocin augmentation for labor have greater blood loss despite higher oxytocin doses. This appears to originate from signal attenuation and desensitization of the oxytocin receptors in a time and concentration dependent manner. Desensitization can occur after four hours of exposure to pitocin. It's also important to note that continued high dose oxytocin exposure in the postpartum period can also lead to acute receptor desensitization, rendering the myometrium less responsive to additional oxytocin, but not other uterotonics such as hemabate or methogen. The awareness of dangers of high dose oxytocin administration and data demonstrating effectiveness of lower oxytocin doses than used historically call into question the safety of practice of injecting 10 to 40 international units of oxytocin into a liter crystalloid solution and infusing this solution at an unspecified rate or often wide open. There are two standardized oxytocin protocols you may consider in order to reduce the oxytocin administration and minimize side effects, all while achieving adequate uterine tone. The first oxytocin administration protocol is coined the rule of threes. Researchers hypothesize that the rule of threes algorithm utilizing oxytocin three international unit boluses with timed uterine tone assessments and a systematic approach to alternative uterotonic agents would reduce oxytocin dose required to obtain adequate uterine tone. Their study involved 60 women undergoing electus cesarean delivery were randomized to receive a low dose bolus or continuous infusion of oxytocin. To blind participants, the rule group simultaneously received intravenous oxytocin, three international units in 3 mLs and a wide open infusion of 0.9% normal saline in a 500 mL bag. The standard care group received intravenous 0.9% normal saline in 3 mLs and a wide open infusion of oxytocin. The wide open infusion was 30 international units of oxytocin in 0.9% normal saline in a 500 mL bag. For the rule group, three units of oxytocin was given as a slow bolus dose at a rate no faster than over 15 seconds. Uterine tone was reassessed again at three and six minutes. If inadequate, an additional dose of oxytocin three unit bolus was administered. If uterine atony persisted after three total doses of oxytocin, it was recommended then to administer a different uterotonic. Adequate uterine tone was achieved with the lower oxytocin doses in the rule bolus administration versus the standard infusion care group. The mean administration of oxytocin in the rule group with the bolus doses was four international units versus the continuous infusion of the standard care group. Their mean administration was 8.4 international units of oxytocin. The rule of threes algorithm did not change uterine tone, maternal hemodynamics, or blood loss. There was no additional uterotonics needed in either group after six minutes. The second standard oxytocin administration protocol involves a standardized infusion. The infusion concentration is 30 units of oxytocin and 500 mLs of normal saline to be administered via a medication infusion pump. Per the standardized continuous oxytocin administration protocol, if the patient has had no prior exposure to oxytocin, you begin the infusion at 300 mLs per hour, which equals 0.3 international units per minute or 18 international units per hour. If that administration rate does not achieve adequate tone, you should increase the infusion to 600 mLs per hour or 0.6 international units per minute, equaling 36 international units per hour. If you still are unable to achieve adequate uterine tone with 600 mLs per hour, you should increase it to 900 mLs per hour, equaling 0.9 international units per minute or a total of 54 international units per hour. If you are still unable to achieve adequate uterine tone at this rate, it is recommended to move on to a different uterotonic. If the patient has had prior exposure to oxytocin due to an induction of labor or an augmentation of labor with pitocin, you should start the infusion at 600 mLs per hour. If you're unable to obtain adequate tone at this rate, then increase the infusion rate to 900 mLs per hour. Again, if you are unable to achieve adequate uterine tone with 900 mLs per hour of the infusion, then you should move on to a different uterotonic. If 900 mLs per hour of your standardized infusion of oxytocin has not achieved adequate tone, it is recommended to administer methogen, 0.2 mg IM, or hemobate, 0.25 mg IM. Once uterine acne is resolved and you administered one full bag of the pitocin, you should start your second bag at 60 mLs per hour or 0.6 IM per minute at 3.6 IM per hour. There is insufficient data to determine when oxytocin administration should occur. Evidence has not shown that it makes a difference in overall blood loss, whether you start the oxytocin immediately after emergence of the infant's shoulder, body, or after the placental delivery. Optimal duration of oxytocin after delivery is also not known, but it has been suggested that after establishment of adequate uterine tone, a minimum of an infusion of three units per hour for up to five hours is recommended because most often postpartum hemorrhage happens within five hours of delivery. In conclusion, I encourage you to consider utilizing evidence-based practice recommendations surrounding oxytocin administration.

oxytocin administration

cesarean delivery

Pitocin

uterine atony

anesthetic considerations