Jeffrey B. Gross

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.

Propofol Depresses the Hypoxic Ventilatory Response during Conscious Sedation and Isohypercapnia

BackgroundPropofol infusion at subanesthetic doses provides reliable conscious sedation. However, the ventilatory effects of sedative doses of propofol have not been established. The current study was conducted to determine the effects of propofol sedation on the hypoxic ventilatory response. MethodsEight healthy, male volunteers received 1 mg ± kg−1 propofol followed by a propofol infusion adjusted to maintain a constant, subanesthetic level of sedation. Hypoxic ventilatory response was measured using an isocapnic rebreathing technique: while keeping Petco2 constant (6 mmHg above prestudy baseline), the authors continuously recorded minute ventilation and tidal volume, as oxygen saturation (Spo2) decreased from 98 to 70%. Hypoxic response determinations were performed before and during propofol infusion, as well as 30 and 60 min after termination of the propofol Infusion. ResultsThe slope of the hypoxic ventilatory response curve (E vs. Spo2) decreased from 0.88 ± 0.15 to 0.17 ± 0.03 1 ± min−1 ± %Spo2−1 during propofol sedation (SE). Thirty minutes after discontinuation of the propofol infusion, slope returned to its prepropofol value. In addition, minute ventilation at Spo2 = 90% decreased during propofol sedation, from 16.1 ± 0.8 to 8.7 ± 0.4 1 ± min−1, accompanied by a similar decrease in tidal volume at Spo2 = 90%, from 1,099 ± 87 to 523 ± 21 ml. Thirty minutes after discontinuation of the propofol infusion, these variables also returned to their prepropofol values. ConclusionsThe authors concluded that propofol infusion for conscious sedation significantly decreases the slope and causes a downward shift of the hypoxic ventilatory response curve measured during isohypercapnia.

Sevoflurane versus isoflurane: induction and recovery characteristics with single-breath inhaled inductions of anesthesia.

Because of its nonpungent odor and low blood-gas solubility coefficient, sevoflurane might be an ideal drug for single-breath inhaled induction of anesthesia. Fifty ASA grade I-III ambulatory surgical patients (18-76 yr old) received a single-breath induction with either 5.0% sevoflurane or 5.0% isoflurane (randomized) in a 1:1 N (2) O/O2 mixture. Anesthesia was maintained with the same anesthetic in 70% N2 O until the end of surgery, when anesthetics were abruptly discontinued. Induction times (loss of eyelash reflex) were similar for sevoflurane (75 +/- 3 s, x +/- SE) and isoflurane (67 +/- 4 s, P = not significant). Sevoflurane patients were less likely to have complications during induction (P < 0.005); coughing occurred more frequently with isoflurane (P < 0.001). During induction, heart rate increased with both sevoflurane (from 73 +/- 3 to 90 +/- 4 bpm, P < 0.05) and isoflurane (from 70 +/- 2 to 92 +/- 2 bpm, P < 0.05); the increase with isoflurane was greater than that with sevoflurane. Times to eye opening for sevoflurane (8.1 +/- 1.0 min) did not differ significantly from those for isoflurane (10.6 +/- 1.3 min). Patients opened their eyes at lower end-tidal minimum alveolar anesthetic concentration (MAC)-fractions of sevoflurane (0.12 +/- 0.01 MAC) than isoflurane (0.15 +/- 0.01 MAC, P < 0.01). During recovery, patients who received sevoflurane felt less clumsy (P < 0.001) and less confused (P < 0.005) but had higher pain scores (P < 0.005) than those who received isoflurane. Sevoflurane is more suitable than isoflurane for single-breath induction, because it produces a smoother induction with a lower incidence of complications and better patient acceptance. (Anesth Analg 1996;82:528-32)

The pharmacodynamic effect of a remifentanil bolus on ventilatory control.

Background In doses typically administered during conscious sedation, remifentanil may be associated with ventilatory depression. However, the time course of ventilatory depression after an initial dose of remifentanil has not been determined previously. Methods In eight healthy volunteers, the authors determined the time course of the ventilatory response to carbon dioxide using the dual isohypercapnic technique. Subjects breathed via mask from a to-and-fro circuit with variable carbon dioxide absorption, allowing the authors to maintain end-tidal pressure of carbon dioxide (PETCO2) at approximately 46 or 56 mmHg (alternate subjects). After 6 min of equilibration, subjects received 0.5 &mgr;g/kg remifentanil over 5 s, and minute ventilation (&OV0312;E) was recorded during the next 20 min. Two hours later, the study was repeated using the other carbon dioxide tension (56 or 46 mmHg). The &OV0312;E data were used to construct two-point carbon dioxide response curves at 30-s intervals after remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (keo), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration–response curve (&ggr;). Results The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l · min−1 · mmHg−1 [−0.12 to 0.66] 2 min after remifentanil (P < 0.001); within 5 min, it recovered to approximately 0.6l · min−1 · mmHg−1, and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mmHg (&OV0312;E50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P < 0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of &OV0312;E50 included keo = 0.24 min−1 (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and &ggr; = 1.74. Conclusions After administration of 0.5 &mgr;g/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.

Epidural Morphine in Children: Pharmacokinetics and CO2 Sensitivity

The effects of epidural morphine (50 µg · kg−1) after abdominal and urologic surgery were studied in 20 children ranging in age from 2 to 15 yr and weighing between 9 and 54 kg. The onset and the duration of analgesia were 30 ± 12 min and 19.5 ± 8 h, respectively (mean ± SD). Side effects were pruritus (4/20), nausea and vomiting (8/20), and urinary retention (4/14). No apnea was observed. Ventilation control was studied in seven children. No significant change in resting respiratory variables occurred after both surgery and epidural morphine injection. However, the slope of the ventilatory response to CO2 was significantly (P < 0.05) decreased after surgery but before morphine, as compared with its preoperative control value (0.84 ± 0.44 versus 1.51 ± 0.72 1 · min−1 · mmHg-1), and remained low for 22 h after epidural morphine (0.90 ± 0.57 1 · min−1 · mmHg−1). Sixty minutes after morphine injection, the plasma morphine concentration was always less than 12 ng-ml−1 in the seven children studied. Pharmacokinetic parameters were similar to those observed after epidural injection of morphine in adults, except for a shorter terminal half-life (73.8 ± 41.6 min) attributed to a greater total body clearance of morphine in the children (28.3 ± 3.4 ml ·min−1 ·kg−1). It is concluded that epidural morphine provides effective and prolonged analgesia in children after abdominal and urologic surgery and that it is associated with prolonged respiratory depression that requires close monitoring for at least 24 h.

Ibuprofen provides longer lasting analgesia than fentanyl after laparoscopic surgery

The authors compared the analgesic efficacy of one dose of oral ibuprofen with that of intravenously administered fentanyl for relief of pain after outpatient laparoscopic surgery. Thirty healthy female patients received either 800 mg of oral ibuprofen preoperatively or 75 micrograms of intravenous fentanyl intraoperatively plus respective intravenous or oral placebos in a randomized, double-blind manner. Patients recorded their degree of pain and nausea in the recovery room, in the same-day surgery stepdown unit, during the ride home, and upon arrival at home. The postanesthesia care nurse recorded the amount of fentanyl and droperidol needed to treat pain and nausea in the recovery room. Patients who received ibuprofen were more comfortable in the stepdown unit (P less than 0.05) and after arrival home (P less than 0.05) than those in the fentanyl group. Additionally, patients who received ibuprofen had lower nausea scores in the step-down unit (P less than 0.05); this may have been related to the lower total fentanyl dose in these patients. The authors conclude that ibuprofen may be a useful alternative to fentanyl for providing postoperative analgesia for outpatient surgery.

Time Course of Ventilatory Depression after Thiopental and Midazolam in Normal Subjects and in Patients with Chronic Obstructive Pulmonary Disease

Using a dual isohypercapnic technique, the authors compared the effect on ventilatory control of midazolam (0.2 mg/kg) and thiopental (3.5 mg/kg) in normal volunteers and in subjects with chronic obstructive pulmonary disease (COPD). In normal volunteers the slope of the CO2 response curve decreased from 1.77 ± 0.16 1*min-1* mmHg-1 (mean ± SEM) to a minimum of 1.14 ± 0.17 1* min-1* mmHg-1 3.5 min after midazolam, returning to 1.32 ± 0.21 1*min-1* mmHg-1 15 min after injection. In the same subjects, the slope of the CO2 response curve fell from 1.89 ± 0.18 1*min-1*ramHg“1 to a minimum of 1.37 ± 0.29 I*min-1* mrnHg-1 one minute after injection of thiopental, returning to 1.69 ± 0.22 1 * min-1* mmHg-1 15 min after injection. These changes were not statistically significant. In subjects with clinical COPD, the slope of the CO2 response curve decreased from 1.89 ± 0.63 1 * min-1* mmHg-1 to a minimum of 0.39 ± 0.19 1*min-1* mmHg-1 two minutes after injection of midazolam (P < 0.05 compared with control), while 15 min after injection, the slope recovered to only 0.62 ± 0.40 1 * min-1* mmHg-1 (P < 0.05 compared with control). In the same subjects, the slope of the CO2 response curve decreased from 1.53 ± 0.17 to a minimum of 0.69 ± 0.25 1*min-1-mmHg-1 0.5 min after injection of thiopental, recovering to 1.47 ± 0.28 1 * min-1* mmHg-1 15 min after injection. This was significantly greater than the corresponding slope after midazolam (P < 0.05). The authors conclude that while the time course of ventilatory depression after thiopental is similar in normal volunteers and in patients with COPD, the ventilatory depression 15 minutes after midazolam is more profound in patients with COPD than in normal subjects.

Quantitative study of degeneration and new growth of axons and synaptic endings in the chinchilla cochlear nucleus after acoustic overstimulation.

To determine if acoustic overstimulation altered synaptic connections in the cochlear nucleus, anesthetized adult chinchillas, with one ear protected by a silicone plug, were exposed for 3 hr to a 108‐dB octave‐band noise, centered at 4 kHz, and allowed to survive for periods up to 32 weeks. This exposure led to cochlear damage in the unprotected ear, mainly in the basal regions of the organ of Corti. The anterior part of the ipsilateral posteroventral cochlear nucleus consistently contained a band of degenerating axons and terminals, in which electron microscopic analysis revealed substantial losses of axons and synaptic terminals with excitatory and inhibitory cytology. The losses were significant after 1 weeks survival and progressed for 16–24 weeks after exposure. By 24–32 weeks, a new growth of these structures produced a resurgence in the number of axons and terminals. The net number of excitatory endings fully recovered, but the quantity with inhibitory cytology was only partially recouped. Neuronal somata lost both excitatory and inhibitory endings at first and later recovered a full complement of excitatory but not inhibitory terminals. Dendrites suffered a net loss of both excitatory and inhibitory endings. Excitatory and inhibitory terminals with unidentified postsynaptic targets in the neuropil declined, then increased in number, with excitatory terminals exhibiting a greater recovery. These findings are consistent with a loss and regrowth of synaptic endings and with a reorganization of synaptic connections that favors excitation.

A comparison of midazolam and diazepam for conscious sedation during colonoscopy in a prospective double-blind study ☆ ☆☆ ★

BACKGROUND Midazolam and diazepam are commonly used for conscious sedation, but their comparative respiratory depressive effects have not been accurately studied. We used a novel real-time, on-line, computerized data acquisition system to compare the two agents in a randomized double-blind study. METHODS One hundred patients undergoing colonoscopy were studied. The maximum end-tidal carbon dioxide tension (PetCO2) and the minimum oxygen saturation by pulse oximetry (SpO 2) were recorded by computer every minute. Patients received meperidine (25 to 50 mg) and incremental doses of either midazolam or diazepam to an identical end point of slurred speech and/or ptosis. Sedation was scored from 1 (unarousable) to 5 (wide awake). RESULTS Sedation scores were 3.6 +/- 0.1 (mean +/- standard error) after each agent. The doses of midazolam and diazepam were 0. 031 +/- 0.002 and 0.106 +/- 0.009 mg/kg, respectively. In the first 45 minutes (PetCO2) was significantly higher with midazolam than with diazepam (p < 0.05). SpO2 was significantly depressed for 80 minutes after each agent, and the number of minutes when the minimum Sp O2 was less than 90% did not differ between the two agents. CONCLUSIONS Midazolam was 3.4 times more potent than diazepam. The duration of oxygen desaturation emphasizes the importance of monitoring SpO2 until ventilation and oxygenation have recovered. Although the degree of hypoxemia was comparable, midazolam led to higher end-tidal carbon dioxide tensions.