Physiologic Changes of Pregnancy

Nervous System

Gin and Chan showed that the median MAC of isoflurane in humans fell 28% during pregnancy (1.075% to 0.775%, p < 0.02) based on Dixon’s up-down method in 20 women (10 per group) [Gin T and Chan MT. Anesthesiology 81: 829, 1994]. They subsequently showed that the MAC of enflurane decreased from 1.65% to 1.15% in comparing 16 pregnant women to 16 controls (30% reduction) [Chan MT et al. Anesthesiology 85: 782, 1996]. Chan and Gin recently presented an ASA abstract suggesting that the ETsevo required to maintain BIS50 was reduced from 1.11% to 0.78% (31% reduction), although there was no correlation between ETsevo and gestation [Chan MT ad Gin T. Anesthesiology 109: A616, 2008]. Sevoflurane has not yet been studied using Dixon’s up-down method.

Epidural vein engorgement (Batson’s plexus) reduces the available epidural and CSF space, such that neuraxial local anesthetic solutions spread to higher levels than usual.


Plasma volume increases 45% at term, RBC volume increases 20%, thus while pregnant patients have increased RBC mass, they appear anemic. Normal hemoglobin is 12 g/dL. During labor, contractions squeeze blood into the systemic circulation, and after delivery, uterine involution autotransfuses 500 cc/blood. Note that clotting factors (I, VII, VIII, IX, X, XII) are elevated, protein S (anticoagulant) is decreased, and there is acquired resistance to protein C. Pregnancy is thus a hypercoagulable state. Also note that both platelet generation and destruction increase, with variable effects. Importantly, 7.6% of term parturients have platelets < 150,000, and 1% have < 100,000 platelets at term. [Burrows RF and Kelton JG. Am J Obstet Gynecol 162: 731, 1990]

Both stroke volume and heart rate increase, the end result being a 40-50% increase in cardiac output by the third trimester (maximal at 24 weeks) – immediately after delivery it can be as high as 80% above normal (150% above pre-pregnancy levels). Increased CO may be detrimental to women with valvular lesions (ex. stenotic lesions). Pregnant women may also develop systolic regurgitation murmurs (usually mitral or tricuspid in origin).

Note that the heart is displaced cephalad and laterally, and the EKG changes of pregnancy include 1) sinus tachycardia 2) other dysrhythmias 3) ST depression 4) T wave flattening 5) LVH and 6) LAD.

Decreases in SVR as result in reduced SBP (avg 8%, as much as 15%) and DBP (avg 20%), likely due to changes in estradiol, progesterone, nitric oxide, and prostacyclin. Increases in venous capacitance and myocardial remodeling attenuate the increased blood volume (i.e., CVP remains constant).

Aortocaval compression can occur in as many as 20% of pregnant women, and can lead to several problems. First, it can lead to maternal hypotension and subsequent fetal acidosis (usually if SBP is 90 – 100 mm Hg for 10 or more minutes), and second, it can further dilate the epidural veins (Batson’s plexus), leading to intravascular injection during epidural anesthesia. Treat with lateral positioning or a right-sided hip wedge.

Maternal Hemodynamic Effects

  • Hematologic: plasma volume increases 45% at term, RBC volume increases 20%
  • Cardiac Output: stroke volume and heart rate increase
  • Vascular resistance: decreases in SVR as result in reduced SBP
  • Venous Return: aortocaval compression can occur in as many as 20% of pregnant women

Note that approximate blood loss is 300-500 cc for a vaginal delivery and 800-1000 cc for a Cesarean section.


Mucosal capillary engorgement during pregnancy can compromise the airway, thus consider using a smaller ETT if standard intubation is required. Avoid nasal intubations if possible (if awake is necessary, attempt an awake oral intubation first). A study of 61 women showed that Mallampati scores increase one grade higher in 33% (and two grades higher in 5%) of women after labor, as compared to before labor [Kodali BS et al. Anesthesiology 108: 357, 2008].

Minute ventilation increases by ~ 50% to make up for increased metabolic demands of the fetus (stimulated by progesterone), most of which is made up by increasing tidal volume (normal pCO2 is 32 mm Hg). FRC falls by ~ 20% due to compressive effects of the fetus, reducing oxygen reserve but increasing the speed at which volatile anesthetics achieve their desired effects. Hyperventilation initially increases PaO2, however in time PaO2 normalizes or even decreases. Note that total lung capacity is relatively unchanged, because the chest circumference actually increases.

Note that during labor, maternal pCO2 may fall as low as 17 mm Hg. This respiratory alkalosis can cause acidosis in the fetus, because the uterus, like the brain, dilates in response to pCO2, thus a hypocapneic uterus can vasoconstrict, potentially causing uteroplacental insufficiency.

In a time of urgency, the mode of preoxygenation is controversial [Baraka AS et al. Anesthesiology 91: 612, 1999] – three studies have shown that 4 deep breaths in 30 seconds is identical to 5 mins of normal breaths, and three others have shown that 4DB/30s is inferior [Benumof JL. Anesthesiology 91: 603, 1999] – Benumof believes that 30s may be inadequate as the lungs are not the only depository for oxygen – while O2 stored by FRC increases by only 300 mL when increasing pre-O2 from 60 to 180 seconds, total body storage increases by 800 mL in that same period of time [Campbell IT et al. Br J Anaesth 72: 3, 1994]. Benumof also states that preoxygenation should be part of the ASA difficult airway algorithm, which it is not, and should be mandatory in all patients as it is impossible to tell when a cannot ventilate cannot intubate situation will arise. Farmery and Roe developed a mathematical model of oxygen delivery and use in the human body, suggesting that when preapnea FAO2 is decreased from 0.87 to 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, and 0.13 (breathing room air) for a healthy 70-kg patient, apnea times to SaO2 = 60% are decreased from 9.90 to 9.32, 8.38, 7.30, 6.37, 5.40, 4.40, 3.55 and 2.80 min, respectively [Farmery AD and Roe PG. Br J Anaesth 76: 284, 1996]. Baraka showed that eight deep breaths for 60s (using a Mapleson D circuit) is superior to 4 deep breaths for 30s (and also to 5 min of non-deep breaths) [Baraka AS et al. Anesthesiology 91: 612, 1999], but this model has to be confirmed using a circle circuit and with standardized flows.

Airway – Rapid Sequence Induction???

Often advocated for patients at risk for aspiration, ex. obstetrical patients, those with intraabdominal processes, etc., several considerations must be taken into account: first, what is the risk of aspiration? Second, how effective are techniques designed to reduce aspiration risk? Third, do these techniques require a tradeoff in terms of airway safety? Fourth, how do different airway equipment affect the risk of aspiration?

Aspiration Risk

Hawkins’ analysis of maternal deaths over a 12 year period found 33 deaths from “aspiration” during general anesthesia, as compared to 37 deaths from either “induction/intubation problems” or “inadequate ventilation” [Hawkins JL et al. Anesthesiology 86: 277, 1997]. Note that these data are pre-LMA in the United States (1990 was the last year included in Hawkins’ analysis, the LMA was not available until 1991).

Data on RSI and Aspiration Risk

A large, metaanalysis of studies showed that there is no data to support or refute the use of RSI to lower aspiration risk, thus the use of RSI can only be recommended on a theoretical basis [Neilipovitz DT and Crosby ET. Can J Anaesth 54: 748, 2007]

RSI and Airway Safety

RSI, which requires paralysis and a mandatory period of apnea (no masking), results in decreased time to hypoxemia and removes the option of spontaneous respiration, at least until SCh has worn off (which can be prolonged in pregnant patients). Thus, careful pre-induction assessment of the airway is indicated and identification of difficult airway management strategies and resources is important – the use of bicitra is based on animal studies which suggest that pH is more damaging than volume if aspiration does in fact occur [James CF et al. Anesth Analg: 63, 665, 1984]. Perhaps consider a nasogastric tube or a cardia blocker [Roewer N. Anesth Analg 80: 378, 1995]

Aspiration Risk and Airway Equipment

In Warner’s study of over 200,000 cases, 67% of cases of aspiration occurred either during laryngoscopy or at the time of extubation [Warner MA et al. Anesthesiology 78: 56, 1993], suggesting that the majority of aspiration events would not be affected by either the use of RSI or the use of an LMA. The ProSeal LMA may be a useful airway adjuvant [Cook TM at el. Br J Anaesth 88: 527, 2002], as its esophageal port allows for suctioning. An unbiased, prospective, comparison of Proseal LMA vs. a traditional LMA is unlikely, as the incidence of aspiration is low and a controlled trial designed to have 80% power and 5% type I error, to detect a 50% reduction in aspiration risk with the PLMA compared with the cLMA would require over 2.5 million elective patients [Cook T. Br J Anaesth 94: 690, 2005]

The Chestnut Editorial: Validity of Regional vs. GA Comparisons

Systematic national studies of anesthesia-related maternal mortality are rare. Anesthesiologists have historically relied on the triennial Report on Confidential Enquiries into Maternal Deaths in the United Kingdom, the most recent of which was published in 2005 [Cooper GM and McClure JH. Br J Anaesth 94: 47, 2005]. The ASA Closed Claims Project has provided valuable information on obstetric injuries but the CCP lacks a denominator, making it impossible to calculate incidence. In 1997, Hawkins et al. presented results of the first national study of anesthesia-related maternal mortality in the United States, a study completed in cooperation with the National Pregnancy Mortality Surveillance System. Unfortunately, critical records were “often incomplete concerning the events surrounding the death.” Furthermore, the data rely on estimates (from workforce surveys in 1981 and 1992) of the number of general and regional anesthetics administered for cesarean section, which implies that the authors underestimated the use of general anesthesia during the years 1985-1990 [Chesnut DH. Anesthesiology 86: 273, 1997].

Airway problems represented the most frequent cause of death among women who died from a complication of general anesthesia. Deaths resulting from regional anesthesia were almost evenly divided between local anesthetic toxicity and high spinal/epidural anesthesia. The case fatality rate for general anesthesia was 2.3 times that for regional anesthesia in 1979-1984, increasing to 16.7 times that for regional anesthesia in 1985-1990.

That said, the validity of the case fatality rates in the Hawkins’ study depends on two assumptions: first, that the authors’ methods were both highly sensitive and specific for identification of anesthesia-related maternal deaths (i.e., the numerator), and second, that the authors have accurately proportioned the number of general anesthetics and regional anesthetics administered for cesarean section. Interestingly, the authors acknowledged that “as many as 37% of maternal deaths are missed due to underreporting on vital statistics records.” Judgments in Hawkins’ study were made without a review of the medical records because these records were unavailable – the type of anesthesia was not identified in one of every five women who died, the type of anesthesia was not identified in two of every five women whose cause of death was listed as cardiac arrest, and the type of obstetric delivery was not identified in one of every eight women who died [Chesnut DH. Anesthesiology 86: 273, 1997]


Given the roughly equal likelihood of death secondary to a cannot-intubate/cannot-ventilate situation or pulmonary aspiration for patients undergoing GA for Cesarean section, coupled with the lack of evidence supporting rapid sequence induction [Neilipovitz DT and Crosby ET. Can J Anaesth 54: 748, 2007], it seems reasonable to consider maintaining spontaneous respiration in patients at high risk for both airway failure and aspiration (ex. obstetric patients). The two major risks in pregnant patients are failed airway and aspiration – the latter has not proven to be a modifiable risk, the former can likely be modified by maintaining spontaneous respiration or considering the use of an LMA as a backup airway (particularly in lower-risk parturients, such as fasting, non-laboring pregnant patients). Thus, the implications of all types of airway management should be strongly considered prior to induction in any high risk patient.


Renal blood flow increases by ~ 50% (identical to changes in cardiac output), thus artificially lowering BUN and creatinine.


LFTs are slightly elevated, which is normal. Serum proteins are decreased, increasing the potency of various medications. Plasma cholinesterase activity decreases ~ 25% at 10 weeks, which can prolong SCh. Coagulation factors increase.


Gastric emptying is reduced by a cephalad pylorus and a progesterone-mediated decrease in gastric motility. Stoelting recommends treating all pregnant women as though they had a full stomach (RSI?), using a cuffed endotracheal tube, and administering non-particulate antacids prior to induction. Note that Hawkins’ analysis of maternal deaths found 33 deaths from aspiration during general anesthesia, as compared to 37 deaths from either “induction/intubation problems” or “inadequate ventilation” [Hawkins JL et al. Anesthesiology 86: 277, 1997]. Note that these data are pre-LMA in the United States (1990 was the last year included in Hawkins’ analysis, the LMA was not available until 1991). Management of difficult airways needs to be planned on an indvidual basis, considering the patient’s characteristics, institutional resources and practitioner skills and experience.

Summary: Clinically RELEVANT Physiologic Changes in Pregnancy


  • Human data (isoflurane and enflurane) suggests that volatile anesthetic requirements are reduced by 28-30%
  • Epidural vein engorgement reduces the available CSF space, extending the spread of subarachnoid injectates


  • EBL is 300-500 cc for vaginal delivery and 800-1000 cc for Cesarean section
  • RBC volume increases 20% (despite “anemia” of pregnancy)
  • SV, HR, and CO increase, while SVR and SBP decrease
  • Aortocaval syndrome occurs in 20% and can 1) lead to fetal acidosis and 2) intravascular injection. Treat by placing patients in the lateral position or by using a right hip wedge.


  • Mucosal capillary engorgement can compromise the airway
  • Increased TV (hypermetabolic fetus) leads to a pCO2 of 32
  • FRC falls by 20%, reducing O2 reserve, but reducing anesthetic time to onset


  • Pregnant patients are at increased risk for aspiration
  • Almost 50% of airway deaths in GA for Cesarean section were due to pulmonary aspiration


  • Plasma proteins decrease, enhancing medication potency
  • Coagulation factors increase, raising the risk of VTE
  • Plasma cholinesterases decrease by ~ 25%, prolonging SCh


  • RBF increases ~ 50% (same as cardiac output), artificially lowering BUN and creatinine