Arterial Stiffness and General Anesthesia Induced Hypotension in Patients on Angiotensin-converting Enzyme Inhibitors
Condition: Hypotension; Arterial Stiffness
MeSH terms: Hypotension
Study type: Observational

Summary: 
      Induction of general anesthesia to the patient could be a challenging period of anesthesia
      management. Due to autonomic system suppression, hemodynamic fluctuation, such as hypotension
      or hypertension, is commonly seen during this period. Furthermore, it has been observed that
      a fraction of patients who develop hypotension may be refractory to vasoactive medications to
      attempt to restore the systemic arterial blood pressure back to an acceptable level.

      Previous studies have shown that patients chronically taking angiotensin converting enzyme
      (ACE) inhibitors have a higher incidence of developing hypotension under general anesthesia
      as well as being refractory to adrenergic vasoconstrictor medications given to help restore
      systemic blood pressure. Interestingly, not all patients taking ACE inhibitors have shown the
      described hemodynamic response after induction of general anesthesia. Therefore,
      investigators are attempting to identify what changes in vascular physiology in those
      patients may contribute to acute refractory systemic hypotension. Specifically, investigators
      wish to explore whether differences in baseline levels of arterial stiffness potentially
      contribute to this phenomenon. Arterial applanation tonometry is a non-invasive technique
      that has been shown to reliably provide indices of arterial stiffness. In the proposed
      project, applanation tonometry will be performed on the right carotid and femoral arteries to
      assess carotid-femoral pulse wave velocity, a surrogate for aortic stiffness. (SphygmoCor
      system, AtCor Medical, Sydney, Australia) The measurement will be obtained before induction
      of general anesthesia in the pre-surgical area. During induction of general anesthesia with
      standard induction agents, brachial blood pressure will be measured by a cuff every minute up
      to 10 minutes after tracheal intubation. A hypotensive response to anesthesia will be defined
      by a systolic arterial blood pressure below 90mmHg upon induction. Hypotensive patients that
      do not respond to vasoconstrictor medications (i.e. requires more than 200 mcg phenylephrine
      to maintain systolic arterial blood pressure above 90 mmHg) will be classified as 'refractory
      hypotensive." Using non-invasive applanation tonometry, we will be able to examine if aortic
      stiffness has a propensity to become refractory hypotension after induction of general
      anesthesia. This information will potentially help identify future patients that might be at
      greater risk of developing refractory hypotension in response to induction of general
      anesthesia.
    

Detailed description: 
      Background: Induction of anesthesia consists with administration of anesthetics followed by
      endotracheal intubation. During the induction of anesthesia moderate hemodynamic disturbances
      (either systemic arterial hyper- or hypo-tension) are common due to concurrent autonomic
      nervous system suppression and from the stress response from endotracheal intubation.
      Previous studies demonstrate that patients chronically treated with angiotensin converting
      enzyme (ACE)-inhibitors have higher incidence of developing hypotension after induction of
      general anesthesia, which typically, can be restored with small doses of adrenergic drugs
      such as phenylephrine (100 to 200 mcg) to acceptable blood pressure levels. However, some
      patients that develop hypotension may be refractory to those medications, which in turn poses
      a significant challenge in controlling the hemodynamics of patients. The consequence of the
      severe hypotension could be canceled surgery, ischemic stroke, myocardial infarction or even
      death.

      Interestingly, this refractory systemic hypotension does not occur in all anesthetized
      patients prescribed ACE inhibitors. Notably, easily treatable systemic arterial hypotension
      after induction of general anesthesia is not a clinical problem. Critical issue arises only
      if the patient under general anesthesia does not respond to therapeutic doses of adrenergic
      agonists. Therefore, identifying patients who will demonstrate refractory hypotension after
      the induction of general anesthesia is a novel idea and has significant clinical implications
      for peri-operative blood pressure control by anesthesiologists.

      Thus, the overall goals of the proposed research will be to use preoperative non-invasive
      measures of vascular stiffness to predict which patients might be at risk for severe
      hypotension that is refractory to adrenergic vasoconstrictor medications following induction
      of general anesthesia in patients chronically treated with angiotensin-converting enzyme
      inhibitors.

      Method/Design: The study will be human subject non-randomized observational study. This study
      will be conducted at day of surgery administration area and main operation room at University
      of Iowa Hospitals and clinics. Arterial stiffness will be measured at day of surgery
      administration area prior to the surgery.

      Carotid-Femoral Pulse Wave Velocity (Aortic Stiffness). Carotid-femoral pulse wave velocity
      (cfPWV) will be determined by applanation tonometry using the Sphygmocor system by
      sequentially recording ECG-gated carotid and femoral artery waveforms. Pulse wave signals
      will be recorded by tonometers positioned at the base of the right common carotid artery and
      over the right femoral artery. The time (t) between the feet of simultaneously recorded waves
      will be determined as the mean of 10 consecutive cardiac cycles. PWV is calculated by the
      system software from the distance between measurement points (D) and the measured time delay
      (t) as follows: cfPWV = D/Δt (m/s) where D is distance in meters and t is the time interval
      in seconds.

      Prior to induction intravenous fluid administration will be restricted to less than 500 ml. A
      standardized protocol will be followed which is commonly used by anesthesia providers. Prior
      to induction of anesthesia, in addition to ASA standard monitors, neuromuscular twitch
      monitor and Entropy monitor will be attached to the patient. Induction agents will include
      1.5mg/kg propofol, 2µg/kg fentanyl, 100mg lidocaine, and 0.6 mg/kg rocuronium of lean body
      weight. Inhaled anesthetic will be sevoflurane at 0.5 MAC with 5L/min of 100% oxygen starting
      at mask ventilation till 10 minutes after tracheal intubation. Blood pressure will be
      measured by a brachial cuff prior to induction and every minute after intubation for 10
      minutes. If the systolic pressure drops below 90 mmHg or more than 25% from baseline, the
      patient will be classified in the study as "Hypotensive." Conversely, if the patient's
      systolic blood pressure does not drop below 90 mmHg more than 25% from baseline within 10
      minutes of intubation, the patient will be classified as "Not Hypotensive." If the patient's
      systolic blood pressure rises above 25% the baseline value, the anesthesiologist will
      administer a bolus of 0.5mg/kg of propofol. This bolus will be repeated after the minute
      blood pressure evaluations until the systolic blood pressure back to the baseline value.
      These patients will be classified as "Not Hypotensive," but the administration of propofol
      will be noted. In attempt to bring systolic blood pressure up to above 90 mmHg or more than
      25% from baseline in "hypotensive" patients, the anesthetic provider will use 100µg
      phenylephrine (or 5mg ephedrine if heart rate < 50bpm) within 10 minutes of intubation. If
      over 200µg phenylephrine (10mg ephedrine) has been used without a return of the systolic
      brachial blood pressure >90 mmHg or more than 25% from baseline, the patient will be
      classified in the study as "Refractory Hypotensive." The study environment will be ended and
      the provider can use whatever vasoactive drugs they deem appropriate, including more
      phenylephrine, ephedrine, epinephrine, norepinephrine, or vasopressin, and/or fluid bolus.
      The total given doses of each vasopressor medication will be recorded. Anesthetic induction,
      blood pressure measurements, and medication to correct low and high blood pressure as
      described above are all part of the patients' standard clinical procedures as performed by
      the anesthesiologist. The patients who required more than 2 times laryngoscopy, required
      other than standard anesthetics, or entropy >70 or <30, will be exclude from data analysis.
    

Intervention name(s): SphygmoCor system
Intervention type(s): Device
Intervention description(s): Carotid-femoral pulse wave velocity (cfPWV) will be determined by applanation tonometry using the Sphygmocor system by sequentially recording ECG-gated carotid and femoral artery waveforms. Pulse wave signals will be recorded by tonometers positioned at the base of the right common carotid artery and over the right femoral artery. The time (t) between the feet of simultaneously recorded waves will be determined as the mean of 10 consecutive cardiac cycles. PWV is calculated by the system software from the distance between measurement points (D) and the measured time delay (t) as follows: cfPWV = D/Δt (m/s) where D is distance in meters and t is the time interval in seconds.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patient who are going under surgery with age between 50 - 85
      
Keywords: angiotensin converting enzyme inhibitor; anesthesia