Toshiaki Nishikawa

Errors in the measurement of cardiac output by thermodilution.

Cardiac output (CO) determination by thermodilution, which was introduced by Fegler in 1954, has gained wide acceptance in clinical medicine and animal experiments because it has several advantages over other methods with respect to simplicity, accuracy, reproducibility, repeated measurements at short intervals, and because there is no need for blood withdrawal. However, errors in determination of CO by thermodilution may be introduced by technical factors and the patients’ pathological conditions. The current review summarizes these issues and provides our recommendations, based on the medical literature published between 1954–1992. To obtain more reproducible and accurate CO values by thermodilution, one should make several determinations (1) by using 10 ml injectate at room temperature for adults and 0.15 ml · kg−1 injectate for infants and children; (2) at evenly spaced intervals of the ventilation cycle; (3) when rapid intravenous fluid administration is discontinued; (4) by observing thermodilution curves so that baseline pulmonary artery temperature drift or the existence of intra- and extra-cardiac shunts are noticed. Finally, CO determination by thermodilution may be unreliable or impossible in patients with low CO slates and tricuspid or pulmonary regurgitation. Since non-invasive CO monitoring has not replaced CO determination by thermodilution, intimate knowledge of this method is crucial for anaesthetists to prevent errors in the management of patients.RésuméLa mesure du débit cardiaque par thermodilution introduite par Fegler en 1954 est largement répandue en clinique et en recherche animale grâce à ses nombreux avantages sur les autres méthodes: simplicité, précision, reproductiblé, répétivité à courts intervalles, absence de prélèvement sanguin. Cependant, dans son application il peut facilement s’introduire des erreurs d’origine technique ou pathologique. La présente revue résume ces questions et propose certaines recommandations, basées sur la littérature médicale publiée entre 1954 et 1992. Pour obtenir des mesures fiables et précises du débit cardiaque par thermodilution, il faut répéter les mesures: 1) avec 10 ml d’injectat maintenu à température de la pièce chez le adulte, 0,15 ml · kg− 1 chez l’enfant; 2) à des moments identiques du cycle respiratoire; 3) après l’arret d’une perfusion rapide de liquide intraveineux; 4) en observant les courbes de thermodilution pour pouvoir tenir compte de la dérive de la température initiale de l’artère pulmonaire et de la présence de shunts intraou extracardiaques. Finalement, le débit cardiaque par hémodilution peut manquer de fiabilité et peut même devenir impossible à mesurer chez les malades dont le débit est bas ou qui souffrent de régurgitation tricuspidienne ou pulmonaire. Comme le monitorage du débit cardiaque non invasif n’a pas encore remplacé la thermodilution, les anesthésistes doivent posséder une connaissance approfondie de cette méthode pour éviter des erreurs thérapeutiques graves.

Effect of nitric oxide synthase inhibition on cerebral blood flow and injury volume during focal ischemia in cats.

Background and Purpose We tested the hypothesis that inhibition of nitric oxide synthase activity in brain before ischemia alters cerebral blood flow and decreases brain injury after 4 hours of middle cerebral artery occlusion in cats. Methods Halothane-anesthetized cats underwent 4 hours of left middle cerebral artery occlusion after they were randomly assigned to receive either intravenous Nω-nitro-L-arginine methyl ester, at a dose that completely inhibited cortical nitric oxide synthase activity (10 mg/kg, n=10), or an equal volume of diluent (10 mL saline, n=10). Serial blood flow measurements were made with radiolabeled microspheres, and injury volume was measured by triphenyltetrazolium staining. Results Blood flow to caudate nucleus and inferior temporal cortex decreased to the same extent in both groups during middle cerebral artery occlusion. Somatosensory evoked potential amplitude was reduced to less than 10% of baseline values in both groups. Injury volume of ipsilateral caudate nucleus in cats pretreated with nitroarginine (52 ± 5%, mean ± SE) was less (P < .05) compared with the saline group (80 ± 4%), whereas ipsilateral cerebral hemispheric injury volume was similar between the two groups (30 ± 6% and 32 ± 4% of hemisphere in saline and nitroarginine groups, respectively). Conclusions These results suggest that inhibition of nitric oxide synthase decreases caudate injury volume at 4 hours of middle cerebral artery occlusion without an alteration in distribution of cerebral blood flow. (Stroke. 1993;24:1717-1724.)

Regional blood flow alterations after bovine fumaryl beta beta-crosslinked hemoglobin transfusion and nitric oxide synthase inhibition.

OBJECTIVES a) To determine whether isovolemic exchange transfusion with cell-free, bovine fumaryl beta beta-crosslinked hemoglobin results in a different pattern of regional blood flow distribution than transfusion with a poor oxygen-carrying, colloidal solution. b) Because of potential nitric oxide scavenging by plasma-based hemoglobin, to determine whether blood flow differences are reduced after nitric oxide synthase inhibition. DESIGN A prospective, randomized design with repeated blood flow measurements within groups. SETTING Experimental physiology laboratory in a university medical center. SUBJECTS Pentobarbital-anesthetized female cats. INTERVENTIONS Three groups of eight cats were studied: a) a control group with no transfusion (hematocrit of 32%); b) an anemia group in which exchange transfusion with an albumin-containing solution reduced hematocrit to 18% over a 40- to 50-min period; and c) a group in which cell-free hemoglobin was exchanged transfused to reduce hematocrit to 18%, without a proportional reduction in oxygen-carrying capacity. Bovine hemoglobin was covalently crosslinked intramolecularly between the 81-lysine residues on the beta-subunits to stabilize the tetramer. Regional blood flow was measured by the radiolabeled microsphere technique before transfusion and at 10, 100, and 180 mins from the start of transfusion. At 190 mins, N omega-nitro-L-arginine methyl ester (L-NAME; 10mg/kg) was infused to inhibit nitric oxide synthase and blood flow was measured 30 mins later. MEASUREMENTS AND MAIN RESULTS Mean arterial pressure was unchanged in the control and albumin-transfused groups. However, mean arterial pressure increased rapidly in the hemoglobin-transfused group. With hemoglobin transfusion, there were marked reductions in blood flow to the intestines, kidneys and adrenal glands. Administration of L-NAME after hemoglobin transfusion failed to increase arterial pressure or cause further reductions in intestinal, renal, or adrenal blood flow. Administration of L-NAME to the control and albumin-transfused groups increased arterial pressure and reduced intestinal, renal, and adrenal blood flows to values attained with hemoglobin transfusion. In contrast, in skeletal muscle and left ventricle, blood flow rates increased in the albumin-transfused group and were greater than those values found in the control group and hemoglobin-transfused group. The greater flow in the albumin-transfused group persisted after L-NAME administration. There was no difference in renal sodium, potassium, or osmolar excretion, or in urine flow between groups. CONCLUSIONS Transfusion with cell-free, bovine crosslinked hemoglobin in cats can selective reductions in blood flow in the intestines, kidneys, and adrenal glands without evidence of renal dysfunction by a mechanism consistent with nitric oxide scavenging. In skeletal and cardiac muscle, the increase in blood flow persisted after nitric oxide inhibition in the albumin group relative to the hemoglobin-transfused group at equivalent hematocrit values. This finding is consistent with compensatory vasoconstriction with hemoglobin transfusion due to improved oxygenation by this oxygen carrier.

Clinical Evaluation of Clonidine Added to Lidocaine Solution for Epidural Anesthesia

The effects of clonidine added to lidocaine solution used for epidural anesthesia were assessed in 92 women scheduled for surgery and premedicated with diazepam 10 mg po. Patients received 18 ml 2% lidocaine with clonidine 5 micrograms.ml-1 (group C-5, n = 26), with clonidine 10 micrograms.ml-1 (group C-10, n = 20), with epinephrine 5 micrograms.ml-1 (group E, n = 26), or plain (group P, n = 20). No significant difference in the number of segments of analgesia was found at any observation period among the four groups of patients. The decreases in mean blood pressure (BP) observed 20 min after epidural injection in those given clonidine (5 +/- 8% for C-5, 10 +/- 11% for C-10, mean +/- SD) were similar to those given plain lidocaine (7 +/- 12%) but significantly less than those given epinephrine (18 +/- 12%, P less than 0.01 vs. C-5 or P). The response of BP to ephedrine given for restoring BP during anesthesia was not attenuated in patients who received epidural clonidine. Heart rate (HR) decreased significantly in patients given clonidine 10 micrograms.ml-1 (7 +/- 8%, P less than 0.01), but not in those given clonidine 5 micrograms.ml-1, whereas HR increased significantly in those given lidocaine plain or with epinephrine (10 +/- 8% and 28 +/- 14%, respectively, P less than 0.01). The incidence of sinus bradycardia was similar among the four groups of patients. Significant differences were also observed in sedation score between clonidine groups and groups P or E; sedation appeared approximately 10-20 min after epidural injection in both clonidine groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral Clonidine Preanesthetic Medication Augments the Pressor Responses to Intravenous Ephedrine in Awake or Anesthetized Patients

To evaluate the possible interaction between clonidine and ephedrine, the authors studied hemodynamic responses to intravenous ephedrine in 80 patients who received either clonidine pre-anesthetic medication of approximately 5 micrograms.kg-1 orally (n = 40) or no medication (n = 40). The patients were studied while they were either awake (n = 40) or anesthetized with enflurane and nitrous oxide in oxygen (n = 40). Hemodynamic measurements were made at 1-min intervals for 10 min after ephedrine 0.1 mg.kg-1 was injected as a bolus. Although the responses to ephedrine were always greater in anesthetized patients, the magnitudes of mean blood pressure increases in patients who received clonidine (10 +/- 8% for awake and 27 +/- 11% for anesthetized subjects, mean +/- standard deviation [SD]) were significantly greater (P less than 0.05) than in patients not receiving clonidine (4 +/- 5% for awake and 17 +/- 11% for anesthetized subjects). The enhanced pressor responses to ephedrine observed in both awake and anesthetized patients in the presence of clonidine may be attributed to increased catecholamine storage at sympathetic nerve endings due to clonidine, enhanced sensitivity of tissue receptors to which ephedrine binds, potentiation of alpha-adrenoceptor mediated vasoconstriction of both agents, or all of these. It is concluded that oral clonidine preanesthetic medication of 5 micrograms.kg-1 does augment rather than attenuate the pressor responses to intravenous ephedrine in patients both prior to and during general anesthesia.

Transient Bilateral Vocal Cord Paralysis after Insertion of a Laryngeal Mask Airway

A laryngeal mask airway (LMA) is used as an alternative to tracheal intubation *RF 1,2* and has been used safely in anesthetized adults and children during spontaneous breathing of controlled ventilation.[3–6] Compared with an endotracheal tube, airway related complications such as sore throat occur

Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in rats.

Background: Dexmedetomidine and hypothermia are known to reduce neuronal injury following cerebral ischemia. We examined whether a combination of dexmedetomidine and hypothermia reduces brain injury after transient forebrain ischemia in rats to a greater extent than either treatment alone.

Nitric oxide synthase inhibition reduces caudate injury following transient focal ischemia in cats.

Background and Purpose We tested the hypothesis that inhibiting nitric oxide production either before or during transient focal ischemia affects early postischemic brain injury. Methods Halothane‐anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 3 hours of reperfusion. Pretreatment groups received either intravenous N&ohgr;‐nitro‐l‐arginine methyl ester (L‐NAME; 10 mg/kg, n=10) or an equal volume of diluent (10 mL saline, n=10) over 30 minutes before ischemia. Posttreatment groups received intravenous L‐NAME (10 mg/kg) over 30 minutes from 45 minutes of ischemia to 15 minutes of reperfusion (n=10) or intravenous L‐NAME (10 mg/kg) plus l‐arginine (200 mg/kg) over the same period followed by continuous l‐arginine infusion (200 mg/kg per hour) for the remainder of reperfusion (n=10). Results Microsphere‐determined blood flow to ipsilateral caudate nucleus and inferior temporal cortex decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the four groups. Triphenyltetrazoliumdetermined injury volume of ipsilateral caudate nucleus in cats treated with L‐NAME before or during ischemia (42±7% and 42±3% of caudate nucleus, respectively; mean±SE) was less (P<.05) compared with that in cats pretreated with saline (72±5%) or cats treated with L‐NAME plus l‐arginine (68±5%). Ipsilateral cerebral hemispheric injury volume was similar among the four groups (23±5%, 13±3%, 18±5%, and 29±5% of hemisphere in groups treated with L‐NAME before ischemia and during ischemia, the saline‐treated group, and the group treated with L‐NAME plus l‐arginine, respectively). Conclusions Inhibition of nitric oxide synthase decreases caudate injury volume from transient focal cerebral ischemia in cats. The beneficial effect is reversed by l‐arginine and is not caused by favorable redistribution of blood flow during ischemia and reperfusion. Because L‐NAME was efficacious when administered at reperfusion, nitric oxide generated during reperfusion appears to contribute to caudate injury. (Stroke. 1994;25:877‐885.)

Simulation of an epidural test dose with intravenous epinephrine in sevoflurane-anesthetized children.

An epidural test dose containing small doses of epinephrine does not produce a reliable increase in heart rate (HR) in children under halothane anesthesia.Because sevoflurane is increasingly used in clinical practice, we designed the present study to determine the hemodynamic responses to, and efficacy of, a simulated IV test dose containing a small dose of epinephrine in sevoflurane-anesthetized children. Sixty ASA physical status I infants and children (4.1 +/- 2.5 yr) undergoing elective minor surgeries were studied during 1.0 minimum alveolar anesthetic concentration of sevoflurane and 60% nitrous oxide in oxygen. The patients were randomly assigned to receive either saline (n = 15), a test dose consisting of 1% lidocaine (0.1 mL/kg) with 1:200,000 epinephrine (0.5 [micro sign]g/kg, n = 15), atropine 0.01 mg/kg followed 5 min later by saline (n = 15), or atropine followed by the test dose (n = 15) via a peripheral vein to simulate intravascular injection of the epidural test dose. HR and systolic blood pressure were recorded every 15 and 30 s, respectively. The test dose increased the HR from 15 to 60 s and from 15 to 90 s without and with atropine, respectively. Mean maximum increases in HR were similar with and without atropine (21 +/- 8 and 22 +/- 6 bpm, respectively). Of 15 children, 7 and 5 developed HR changes <20 bpm after the test dose with and without atropine, respectively, whereas all children who received saline had an increase in HR <20 bpm. No dysrhythmia occurred during the study. Our results indicate that an epidural test dose containing epinephrine is unreliable based on the conventional HR criterion (positive if >or=to20 bpm increase), but reliable on the modified HR criterion (positive if >or=to10 bpm increase) in children anesthetized with sevoflurane. IV atropine before the test dose injection did not improve the efficacy based on the conventional HR criterion. Because test doses of epinephrine-containing solution are used to determine whether an epidural catheter is intravascular, it is important to define the optimal test dose under sevoflurane anesthesia. Implications: We found that during sevoflurane anesthesia in children, a heart rate increase >or=to10 bpm and a systolic blood pressure increase >or=to15 mm Hg, when preceded by atropine, may be reliable indicators for detecting intravascular injection. (Anesth Analg 1998;86:952-7)

Oral clonidine premedication enhances the quality of postoperative analgesia by intrathecal morphine

Since clonidine potentiates the analgesia by morphine, the current study was performed to investigate whether oral clonidine premedication would enhance the postoperative analgesia by intrathecal morphine.Twenty-six patients, aged 37-60 yr, scheduled for abdominal total hysterectomy under spinal anesthesia, were studied. Patients were randomly allocated to one of two groups; the clonidine group (n = 13) received oral clonidine approximately 5 micro gram/kg, and the control group (n = 13) received no clonidine. All patients received hyperbaric tetracaine 12 mg dissolved in 10% dextrose and morphine 0.2 mg for spinal anesthesia. We measured duration of analgesia (time to the first request for supplemental analgesics) and motor block. We also recorded the total number of injections of supplemental analgesics, and intensity of postoperative visual analog pain scores, nausea, and pruritus for 48 h after intrathecal administration. Duration of analgesia in the clonidine group was longer than the control group (2017 +/- 263 vs 1190 +/- 199 min, mean +/- SEM; P < 0.05). Although there was no difference in the total number of injections of supplemental analgesics (1.1 +/- 0.4 and 2.2 +/- 0.3 in the clonidine and control groups, respectively), the number of patients not requiring supplemental analgesics during the entire study period was larger in the clonidine group than the control group (six patients versus one patient; P < 0.05). There were no differences at any observation point between groups in visual analog pain scores, or the incidence of nausea and pruritus. Oral clonidine preanesthetic medication enhances the postoperative analgesia of intrathecal morphine plus tetracaine without increasing the intensity of side effects from morphine. (Anesth Analg 1996;82:1192-6)