Christian M. Alexander

Principles of pulse oximetry: theoretical and practical considerations.

Continuous monitoring of arterial oxygen saturation with a pulse oximeter is rapidly becoming a standard of anesthesiology practice (1). Because of the tremendous potential market, more than 20 manufacturers now produce pulse oximeters. As one might expect, there have been many unsubstantiated claims and couterclaims regarding those features and capabilities that distinguish one oximeter from another. The purpose of this communication is threefold: (a) to review the underlying principles of pulse oximetry and the limitations they impose, (b) to provide a basis for assessing pulse oximeters to be used in a particular application, and (c) to make available the results of a comparative evaluation of nine widely marketed pulse oximeters (Table 1).

Sedative Doses of Midazolam Depress Hypoxic Ventilatory Responses in Humans

The effect of midazolam on the hypoxic ventilatory response of eight healthy volunteers was examined during isocapnic rebreathing. The magnitude of the slope of the ventilatory response to hypoxia (&OV0312;E vs SaO2) decreased from 1.48 ± 0.24 to 0.70 ± 0.13 L·min−1 ± %SaO2−1 (&OV0398; ± SE, P < 0.005) after midazolam 0.1 mg/kg IV. The calculated ventilation at an arterial saturation of 90% also decreased from 28.6 ± 4.4 to 19.9 ± 2.7 L/min (P < 0.05). Before midazolam, hypoxia to an SaO2 of 75 ± 2% was associated with a 23 ± 3 beatslmin increase in heart rate; after midazolam, the increase in heart rate with hypoxia was only 4 ± 2 beatslmin (P < 0.003). Additionally, a double-blind crossover study evaluated the effect of phy-sostigmine on awareness and hypoxic ventilatory response after midazolam. The change in hypoxic response slope after physostigmine 2.0 mg IV (an increase of 0.28 ± 0.34 L-min−1 ± %SaO2−1) did not differ significantly from that after placebo (an increase of 0.03 ± 0.22 L-min−1 ± %SaO2−1), although physostigmine significantly increased awareness. It is concluded that a sedative dose of midazolam depresses hypoxic ventilatory response and attenuates the hyperpnea andtachycardia associated with hypoxemia. Furthermore, physostigmine-glycopyrrolate reversal of midazolam-induced sedation was associated with nausea (five subjects), vomiting (three subjects), and tachycardia without reversal of the depressed hypoxic ventilatory response.

Influence of isoflurane on hypoxic pulmonary vasoconstriction in dogs

The authors studied the influence of locally administered isoflurane anesthesia on the pulmonary vascular response to regional alveolar hypoxia (hypoxic pulmonary vasoconstriction [HPV]) over a range of cardiac outputs (COs) in seven mechanically ventilated, closed-chest dogs. The right lung was ventilated with 100% O2 throughout the study. The left lung was ventilated with either 100% O2 (normoxia) or an hypoxic gas mixture (hypoxia). Different alveolar concentrations of isoflurane (0, 1, and 2.5 MAC) were administered to the left lung in a randomized sequence. The CO was altered by opening and closing surgically produced arteriovenous fistulae, at all isoflurane concentrations, and by hemorrhage at 0 MAC isoflurane. The magnitude of the HPV response was measured by differential CO2 elimination in the absence of isoflurane and by venous admixtures in all phases. During normoxia, the left lung effective flow (&OV0422;L%) measured from differential CO2 excretion was 39.9 ± 1.2% of the total blood flow and decreased to 18.8 ± 2.6% when ventilated with the hypoxic gas mixture. Venous admixture (&OV0422;VA/&OV0422;T%) was significantly correlated with &OV0422;L% during hypoxic ventilation in the absence of isoflurane. &OV0422;VA/&OV0422;T% was 22.3 ± 2.7% during hypoxia with normal CO, and it increased significantly to 27.7 ± 1.1% when the CO was increased 43%. It was not significantly altered (23.6 ± 3.6%) when the CO was decreased by 54%. Isoflurane 2.5 MAC significantly increased &OV0422;VA/QT% during hypoxic ventilation of the left lung to 33.9 ± 2.6% with low CO and 35.4 ± 1.7% with normal CO. Isoflurane 1 MAC increased &OV0422;VA/QT% to 27.2 ± 2.7% with normal CO and 28.1 ± 2.6% with high CO. Comparing the effects of the different concentrations of isoflurane on &OV0422;VA/&OV0422;T% during left lung hypoxia under the same conditions of CO, mixed venous and alveolar oxygen tension, and pulmonary artery and pulmonary artery occlusion pressures revealed a significant direct effect of isoflurane dose such that: (% depression of HPV) = [22.8(% alveolar isoflurane) – 5.3]. The ED50 for this response was 2.4% alveolar isoflurane. The authors conclude that isoflurane directly depresses HPV and that secondary influences of the anesthetic action should be considered in the interpretation of the action of inhalational agents on this response in vivo.

Time Course and Responses of Sustained Hypoxic Pulmonary Vasoconstriction in the Dog

The stability of the pulmonary blood pressure and flow response to alveolar hypoxia (hypoxic pulmonary vasoconstriction or HPV) was studied in six pentobarbital anesthetized, mechanically ventilated open-chested dogs. Aortic and left pulmonary artery blood flows; systemic and pulmonary arterial, central venous, left atrial, and airway pressures; hemoglobin; arterial and mixed venous blood gases were measured. The right lung was ventilated continuously with 100% oxygen, while the left lung was ventilated alternately with 100% O2 (prehypoxia control phase), an hypoxic gas mixture containing 4% O2, 3% CO2, balance N2 for 4 h, or 100% O2 (post-hypoxia control phase). Hypoxic ventilation of the left lung resulted in an immediate and sustained decrease in left lung blood flow (&OV0422;L%) from 39.0 ± 1.8% (mean ± SE) to 9.9 ± 3.6% at 15 min of hypoxic ventilation. &OV0422;L% remained decreased and did not vary significantly during the 4 h of hypoxia. Venous admixture correspondingly was increased and Pao2 decreased by hypoxic ventilation and did not vary significantly during the 4 h of hypoxia. All variables returned to control levels upon reestablishing ventilation with 100% O2.While the maximal reduction in &OV0422;L% with left lung hypoxic ventilation was identical to that observed during atelectasis previously in our laboratory, the time course of the response was different. The response to hypoxia was maximal by 15 min, however, &OV0422;L% decreased more slowly during atelectasis, where the maximal reduction was observed by 60 min. The present study therefore demonstrated that hypoxic ventilation of the left lung yielded an immediate and sustained decrease in left lung blood flow for 4 h. The stability of the HPV response probably was accounted for by the lack of such confounding factors as respiratory alkalosis, severe systemic hypoxemia, and increased cardiac output.

Diphenhydramine Enhances the Interaction of Hypercapnic and Hypoxic Ventilatory Drive

Background:Although diphenhydramine is frequently used to treat pruritus and nausea in patients who have received neuraxial opioids, there are no data regarding its effect on ventilatory control. We conducted the current study to evaluate the effects of diphenhydramine on hypercapnic and hypoxic ventilatory control in healthy volunteers. Methods:First, we measured the steady-state ventilatory response to carbon dioxide during hyperoxia with an end-tidal carbon dioxide tension of 46 or 54 mmHg (alternate subjects) in eight healthy volunteers. We then determined the hypoxic ventilatory response during isocapnic rebreathing at the same carbon dioxide tension. After a 10-min recovery period, we repeated the steady-state and hypoxic ventilatory response measurements at the other carbon dioxide tension (54 or 46 mmHg). Ten minutes after subjects received diphenhydramine 0.7 mg·kg-1 intravenously, we repeated this sequence of ventilatory measurements. Results:Under hyperoxic conditions (inspired oxygen fraction > 0.5) diphenhydramine did not affect the ventilatory resposnse to hypercapnia. Similarly, at an end-tidal carbon dioxide tension of 46 mmHg, neither the slope nor the position of the hypoxic ventilatory response curve changed significantly after diphenhydramine. However, at an end-tidal carbon dioxide tension of 54 mmHg, the slope of the hypoxic ventilatory response increased from 1.28 ± 0.33 to 2.13 ± 0.61 1·min-1 · %Spo2-1 (mean ± standard error), and &OV0312;E at an arterial hemoglobin oxygen saturation of 90% increased from 31.2 ± 3.1 to 43.1 ± 5.4 1·min-1). Conclusions:We conclude that although it did not affect the ventilatory response to carbon dioxide during hyperoxia or the ventilatory response to hypoxia at an end-tidal carbon dioxide tension of 46 mmHg diphenhydramine augmented the hypoxic response under conditions of hypercapnia in our young healthy volunteers. Although these findings may help to explain the apparent safety of diphenhydramine, they may not be applicable to debilitated patients or those who have received systemic or neuraxial ventilatory depressants.

Awakening concentrations of isoflurane are not affected by analgesic doses of morphine.

A randomized, double-blind study was performed to determine how morphine 0.1 mg/kg IV, or placebo administered 80 ± 11 (&OV0398; ± SE) minutes before the end of surgery affect recovery from isoflurane/oxygen anesthesia. End-tidal isoflurane remainedconstant at 1.10 ± 0.02% (&OV0398; ± SE) in both groups intraoperatively, and no other anesthetics were given after the administration of the morphine or placebo. Duration of anesthesia did not differ significantly between the morphine (172 ± 7 minutes) and placebo (163 ± 18 minutes) groups. Times from discontinuation of isoflurane until eye-opening in response to verbal command were similar in the morphine (19 ± 2 minutes) and placebo (22 ± 3 minutes) groups. At the time of eye-opening, end-tidal isoflurane concentrations did not differ between subjects receiving morphine (0.20 ± 0.02%) and placebo (0.18 ± 0.01%). It is concluded that the awakening concentration (MAC-awake) during recovery from isoflurane anesthesia is approximately 0.19% and is not affected by analgesic doses of morphine.

Hypoxic Pulmonary Vasoconstriction Is Not Potentiated by Repeated Intermittent Hypoxia in Closed Chest Dogs

Hypoxic pulmonary vasoconstrictor (HPV) responses were measured with repeated intermittent hypoxic challenges in eight non-traumatized closed chest dogs anesthetized with pentobarbital. The right lung was ventilated continuously with 100% O2 while the left lung was either ventilated with 100% O2 (control) or ventilated with a gas mixture containing 3–4% O2 (hypoxia). Mean per cent left lung blood flow for all four normoxic periods was 43.1 ± 1.5% (mean ± SE) of the total blood flow by the SF6 excretion method and 40.8 ± 1.1% by the differential CO2 excretion method, corrected for the Haldane effect. With hypoxic ventilation, flow diversion from the hypoxic lung was maximal with the first exposure and did not change subsequently with a total of four alternating exposures to normoxia and hypoxia. Flow diversion during hypoxia was approximately 50.5 ± 2.4% by the SF6 method and 50.3 ± 3.5% by the Vco2 method. This result contrasts with the increasing flow diversion response with intermittant hypoxic exposure that has been reported in animals exposed first to thoracotomy and surgical dissection. It is concluded that in the absence of surgical trauma the initial response to hypoxia is maximal and is not potentiated by repeated hypoxic stimulation.

Slow injection does not prevent midazolam-induced ventilatory depression.

To determine whether the risk of midazolam-induced ventilatory depression is related to the rate of midazolam administration, we compared the effect of rapid (over 15 s) and slow (over 5 min) administration of midazolam (0.1 mg/kg IV) on the hypercarbic ventilatory response of 10 healthy volunteers. During the first 5 min after the start of midazolam injection, the slope of the ventilatory response to CO2 was significantly lower when the subjects received midazolam rapidly (P less than 0.001). However, after completion of the infusion (between 5 and 20 min), depression of the CO2 response curve slope was independent of the rate of midazolam administration. Similarly, although minute ventilation and tidal volume measured at an end-tidal CO2 tension of approximately 46 mm Hg decreased more quickly after rapid administration of midazolam (P less than 0.001), these variables did not differ significantly between the two rates of administration once the slow infusion was complete. These results suggest that slow administration of midazolam provides no independent protection from respiratory depression.

The effect of pleural pressure on the hypoxic pulmonary vasoconstrictor response in closed chest dogs.

The effect of intrapleural pressure on the hypoxic pulmonary vasoconstrictor (HPV) responses to atelectasis and hypoxia were measured in two groups of anesthetized closed chest dogs. The right lung was continuously ventilated with 100% O2. The left lung was initially ventilated with 100% O2, (hyperoxia) but subsequently underwent either reabsorption atelectasis (atelectasis; group I) or ventilation with a hypoxic gas mixture (hypoxia; group II). The mean intrapleural pressure in the left hemithorax was 5.4 cm H2O during hyperoxia, but with left lung atelectasis decreased significantly to −3.8 cm H2O by 15 minutes and to −4.2 cm H2O by 90 minutes. Venous admixture (%VA) increased significantly from 10.3% during hyperoxia to 33.2% at 15 minutes of left lung atelectasis and to 34.6% at 90 minutes. However, after sternotomy with the left lung still atelectatic, the %VA decreased significantly to 25.4%. For the hypoxia group, %VA increased significantly from 9.2% during hyperoxia to 29.9% at 15 minutes of left lung hypoxia and 25.1 % at 90 minutes. HPV diverted blood flow away from both atelectatic lung and hypoxic lung. However, due to the negative intrapleural pressure generated during left lung resorption atelectasis when the chest was closed, HPV was less effective during atelectasis than during hypoxia.

The Influence of Halothane and Isoflurane on Pulmonary Collateral Ventilation

The effects of halothane and isoflurane on hypocapnic increases in pulmonary collateral resistance were studied in dogs. A bronchoscope with a double lumen catheter in the suction port obstructed a peripheral airway and allowed gas to flow out of the isolated segment of lung only via collateral channels. The collateral gas flow (&OV0312;coll) was measured with a flowmeter and delivered through one lumen of the catheter, while the other lumen measured distal pressure (Pb). At FRC, the resistance to collateral ventilation (Rcoll) was calculated as Rcoll = Pb/Vcoll. The rest of the lung was ventilated with air, while air (hypocapnia), 10% CO2 in air, or air and halothane or isoflurane were delivered to the isolated segment. A measurement of resistance was made after 4 min of test gas flow. For each segment, when air replaced 10% CO2, the average increase in Rcoll was calculated and called Rmax. When 10% CO2 in air was infused into segments the mean Rcoll (n = 50) was 0.0196 ± 0.0022 cmH2O·ml−1 · min. This increased to 0.0285 ± 0.0031 cmH2O · ml−1 · min (mean ± E) when air was infused, a mean increase in resistance of 52 ± 3%. When halothane or isoflurane was added to air the hypocapnic increase in Rcoll was attenuated with a 50% decrease at 1.3% (1.4 MAC and 0.8 MAC, respectively). These two inhalational anesthetics reduce active changes in the flow resistance to collateral ventilation. When collateral resistance acts to adjust ventilation perfusion deviations, this action of halothane and isoflurane may make this regulation less effective.