Uterotonics
Oxytocin
Whereas true oxytocin, which is similar to vasopressin, causes hypertension, synthetic oxytocin (Pitocin) causes hypotension and should be given slowly (ideally ~ 40U in at least 500 cc crystalloid over 10 mins). A bolus of 10U synthetic oxytocin was shown to lower MAP 40%, and SVR 59% (thus cardiac output actually increased), an effect not seen when infused over 10 minutes [Secher NJ et al. Acta Obstet Gynecol Scand 57: 97, 1978]. In large doses Pitocin can take on some characteristics of vasopressin (ex. antidiuretic effects).
Ergot Alkyloids
Ergonovine and methylergonovine (Methergen 0.2 mg IM) are second line after oxytocin, however they have been reported to cause ICH due to hypertension and peripheral vasoconstriction and are contraindicated in the presence of preeclampsia.
Prostaglandins
PGF2alpha or 15-methyl analog of PGF2alpha called carboprost (Hemabate, 0.25 mg IM or into myometrium) is third line, and in addition to hypertension may cause bronchoconstriction and pulmonary hypertension.
Tocolytics
Magnesium Sulfate
Potentiates NMBDs (use a nerve stimulator) and reduces MAC (NMDA antagonist, also keep in mind that it can cause neurologic depression [lethargy], respiratory depression, etc. Reversed with calcium). 4-6 g over 20 mins, then 2g/hr, goal 6-8 mg/dL. Can cause Floppy Baby Syndrome. Causes mild uterine artery dilation which, in animal models, has been shown to increase uterine artery blood flow. [Vincent RD Jr et al. Anesthesiology 74: 77, 1991]
Beta Agonists
Terbutaline can cause agitation, restlessness, tremors (similar to other beta-agonists, opposite of older beta blockers). Arrhythmogenic. Hypotension. Pulmonary edema (incidence is 5%), hyperglycemia (simulated stress response), hypokalemia (which may prolong non-depolarizing NMBDs).
CCBs
Nifedipine has been used with some success but must be used with caution when combined with volatile anesthetics (potentiates myocardial depression) and magnesium (cardiovascular collapse may occur). Doppler imaging of 21 women showed that fetal arterial and uterine artery Doppler parameters were not changed by nifedipine therapy. [Guclu S et al. Ultrasound Obstet Gynecol 24: 761, 2004]
Antihypertensives
Beta-Blockers
Labetalol effects peak at 35 minutes in the parturient. 0.8 mg/kg has been shown to decrease MAP by 18% without affecting uterine or fetal flow velocity waveforms [Pirhonen JP et al. J Perinat Med 19: 167, 1991]. In parturients taking propranolol (non-specific beta blocker), beware prostaglandin F2a and morphine, all of which can potentially increase airway resistance synergistically. Esmolol has caused extreme fetal bradycardia.
Hydralazine
Arterial vasodilator, relatively long onset time, may cause reflex tachycardia. Interestingly, a small sheep study comparing nitroprusside to hydralazine following phenylephrine-induced hypertension showed that hydralazaine actually increased uterine blood flow. (and nitroprusside produced no change) [Ring G et al. Obstet Gynecol 50: 598, 1997]
CCBs
Nifedipine has been used with some success but must be used with caution when combined with volatile anesthetics (potentiates myocardial depression) and magnesium (cardiovascular collapse may occur). Doppler imaging of 21 women showed that fetal arterial and uterine artery Doppler parameters were not changed by nifedipine therapy. [Guclu S et al. Ultrasound Obstet Gynecol 24: 761, 2004]
Nitroglycerine
Venodilator (with some arterial effects), also serves as a uterine relaxant. Has been shown in animal studies to have increase uterine flow in the setting of phenylephrine-induced hypertension [Craft JB Jr et al. Anesth Analg 59: 494, 1980]
Nitroprusside
Predominantly arterial vasodilator, highly titrateable, evidence regarding an association with fetal demise is inconclusive at best [Sass N et al. Sao Paulo Med J 125: 108, 2007]. A small sheep study comparing nitroprusside to hydralazine following phenylephrine-induced hypertension showed that and nitroprusside produced no change in uterine blood flow. [Ring G et al. Obstet Gynecol 50: 598, 1997]
Sympatholytics
Alpha-methyldopa, reserpine, and guanethidine may deplete norepinephrine, making ephedrine ineffective if needed (use PHE instead).
Vasopressors
Epinephrine
Test dose (15 ucg) has been shown to cause a transient (less than three minutes) decrease in sheep uterine blood flow. [Hood DD et al. Anesthesiology. 64: 610, 1986]
Phenylephrine
In a hypotensive, hypoxemic sheep model, phenylephrine was inferior to ephedrine in terms of uterine and placental hemodynamics and fetal lactate concentrations. [Erkinaro T et al. Br J Anaesth 96: 231, 2006]
Anesthetic Agents
Propofol
In animal studies (sheep), propofol at 2 mg/kg followed by an infusion does not appear to affect maternal or fetal mean arterial pressure, heart rate, base excess, fetal heart rate variability, or uterine blood flow. [Alon E et al. Anesthesiology 78: 562, 1993]
Ketamine
0.7 mg/kg in sheep resulted in a 7% increase in MAP, a 16% increase in cardiac output, although the uterine blood flow remained constant. [Craft JB et al. Am J OBstet Gynecol 146: 429, 1983]
Volatile Anesthetics
While volatile anesthetics decrease MAP, they likely that at normal obstetric doses (often < 1.0 MAC) they do not result in decreased uterine blood flow. A study of 16 sheep anesthetized with halothane and isoflurane showed maintenance of uterine blood flow with MAC ranging from 1.0 to 1.5, although at MAC 2.0 uterine blood flow began to fall off, leading to fetal compromise [Palahniuk RJ and Shnider SM. Anesthesiology 41: 462, 1974]
Others
Antibiotics
One should assume that antibiotics prolong muscle relaxation in the pregnant population (neomycin, streptomycin, gentamicin, kanamycin, polymixin A and B, colistin, tetracycline, and clindamicin have all been shown to increase the duration of d-Tubocurarine).
Antiepileptics
Pharmacokinetics are markedly altered, in general parturients need higher doses of antiepileptics because volume of distribution (dose/[drug]) is increased. Note that many of these agents may decrease fetal vitamin-K-dependent clotting factor synthesis.
Psychotropic Medications
Antipsychotics
Generally enhance the effect of opioids and may act as alpha-antagonists.
Antidepressants
SSRIs are known to cause clotting abnormalities thus coagulation data should be assessed in these patients. Some SSRIs have alpha-blocking activity. SSRIs can potentiate benzodiazepines, and when combined with meperidine may lead to serotonin syndrome. TCAs intensify the response to direct-acting vasopressors, atropine, and opioids, while at the same time curtailing the response to indirect acting vasopressors (ex. ephedrine). MAOIs have the opposite effect on vasopressors, potentiating (sometimes catastrophically) ephedrine and thus mandating that only direct-acting agents be used. Meperidine can also interact with MAOIs and should probably be avoided in these patients.
Lithium
May prolong the activity of depolarizing and non-depolarizing NMBDs, as well as barbiturates.
Recreational Drugs
Chronic cocaine use will decrease release of NE, however acute use still causes tachycardia and hypertension, which should be treated with labetalol (to avoid unopposed alpha stimulation). Amphetamines result in increased MAC requirements for patients who abuse them chronically.
