Anesthetic management of patients undergoing unilateral video-assisted lung reduction for treatment of end-stage emphysema.

OBJECTIVES: Nonanatomic resection of peripheral areas of lung is being performed via sternotomy for the treatment of end-stage emphysema. Recent technologic advances have allowed the resection of lung tissue using video-assisted thoracic surgery (VATS) techniques. The study was performed to document the physiologic changes that occur during unilateral VATS lung reduction in hopes of determining appropriate monitoring and intraoperative management strategies. DESIGN: Prospective trial of unilateral VATS lung reduction. SETTING: Tertiary care university hospital. PARTICIPANTS: Twenty patients with end-stage emphysema. INTERVENTIONS: Participants underwent unilateral VATS lung reduction. MEASUREMENTS AND MAIN RESULTS: Invasive hemodynamic monitoring was performed using radial and pulmonary artery catheters. Hemodynamic and respiratory gas exchange data were collected at four intraoperative points: (1) supine, two-lung ventilation; (2) lateral decubitus, two-lung ventilation; (3) lateral decubitus, one-lung ventilation, and (4) end of surgery, supine, two-lung ventilation. Data were compared with that collected at the first point. Patients tolerated lengthy surgical procedures and remained hemodynamically stable with no episodes of hypoxemia requiring treatment. Extubation was tolerated by 19 of 20 patients at the conclusion of surgery without further requirement of mechanical ventilation. CONCLUSIONS: VATS lung reduction under general anesthesia with one-lung ventilation is well tolerated. Permissive hypercapnia was well tolerated by all patients. Early extubation can be routinely accomplished in these patients.

Noninvasive measures of radiolabeled dextran transport in in situ rabbit lung.

UNLABELLED: Dextrans are nontoxic and can be obtained in a wide variety of molecular weights. The purpose of this study was to label 6-kDa and 40-kDa dextrans with gamma- (99mTc) and positron- (18F) emitting radioisotopes and monitor their transport across the pulmonary microvascular barrier. METHODS: External scan measurements for radiolabeled uncharged dextrans, albumin and red blood cells were obtained in eight blood-perfused in situ rabbit lung preparations. After 3 hr of external scanning, the lungs were removed for postmortem and extravascular distribution volume calculations. Extravascular distribution volumes were obtained in six additional rabbits following 4 hr of dextran perfusion to compare the effect of time. The normalized slope index (NSI), a measure of transvascular transport rate, was calculated for each diffusible tracer. RESULTS: The mean NSI for albumin (0.001676 +/- 0.000537 min-1) was significantly lower than NSI for the 40-kDa dextran (0.002303 +/- 0.0005426 min-1) as well as the 6-kDa dextran (0.004312 +/- 0.001134 min-1). The difference between the 6-kDa and the 40-kDa dextrans was also significant. After 4 hr of equilibration, distribution volumes were not significantly different than those obtained at 3 hr. CONCLUSION: Dextrans can be radiolabeled with gamma and positron emitters and small dextrans traverse the lung microvascular barrier more rapidly than albumin. Our results suggest that the use of small dextrans rather than albumin can reduce scan times in clinical applications and minimize motion artifact associated with the noninvasive gamma detection method.

Effect of hydroxyethyl starch on alveolar flooding in acute lung injury in dogs.

The efficacy of hydroxyethyl starch (HES) in limiting alveolar flooding after acute lung injury was investigated using ethchlorvynol (ECV)-induced low pressure pulmonary edema in dogs. Harvested autologous plasma (PL) (control, n = 8) or 6% HES (n = 8) was infused (25 ml/kg) along with packed cells to result in an isovolemic, normochromic preparation before the administration of ECV. Extravascular thermal volume significantly increased after ECV administration in both groups of animals (6.6 to 13.4 ml/kg in PL, 6.5 to 15.0 ml/kg in HES). Systemic arterial PO2 decreased from 216 +/- 4 to 113 +/- 20 mm Hg, and venous admixture increased from 2.8 to 12.8% in the PL group but was not significantly changed in the HES group (219 +/- 5 to 203 +/- 8 mm Hg, and 2.9 to 4.4%, respectively). Epithelial lining fluid volumes after ECV administration increased in both groups but were elevated in the PL group to a greater extent than in the HES group (13.5 ml in HES versus 24.8 ml in PL). In the HES group there appeared to be no difference in the ability of plasma proteins to move across the alveolar epithelium. These results suggest that HES attenuates the flooding of the alveolar space and the resulting alterations in gas exchange during the development of low pressure pulmonary edema. The replacement of the plasma proteins with HES and the apparent inability of HES to cross the epithelial barrier into the alveoli may account for the protective effect of HES in these experiments.

Protective effect of 2-chloroadenosine on lung ischemia reperfusion injury.

Reperfusion following ischemia yields an inflammatory response characterized by polymorphonuclear leukocyte (PMN) influx, inflammatory mediator release, microvascular permeability alteration, and protein-enriched fluid transudation. Evidence has accumulated suggesting that low-dose adenosine may "down-regulate" the PMN response. This study evaluated the effects of an adenosine analogue, 2-chloroadenosine (2CA), on ischemia-reperfusion (IR) injury in rabbit lungs. In these experiments the left pulmonary hilum was skeletonized, obliterating the bronchial circulation, and the left pulmonary artery and vein were occluded for 1 min for the sham ischemia (SI-V) group or for 1 hr for the ischemia (I-V) and 2CA-treated (I-A) groups. The left lung was inflated with nitrogen during the ischemic period. Saline (SI-V and I-V groups) or 2CA (I-A group) infusions were begun prior to and during the reperfusion period. After 4 hr of reperfusion and restored ventilation, selective left lung physiologic measurements and bronchoalveolar lavage (BAL) were performed. Groups (N = 8/group) were compared using analysis of variance. The I-A group demonstrated a significantly lower mean pulmonary artery pressure and higher cardiac output than the I-V group. Pulmonary vascular resistance was significantly elevated in group I-V compared to group I-A. A significantly greater alveolar WBC influx and protein transudation (BAL/plasma albumin) occurred in the ischemic group compared to the 2CA-treated animals and sham controls. Decreased PaO2 and increased venous admixture were noted in the ischemic group, but did not reach significance when compared to the 2CA group.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of increased pulmonary microvascular permeability induced by FMLP in isolated rabbit lungs.

We observed that the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L- phenylalanine (FMLP) induced pulmonary edema when polymorphonuclear leukocytes (PMNs) were added to isolated constant-flow buffer-perfused rabbit lungs. This study was designed to test the hypothesis that PMNs activated by FMLP induced lung injury by the modulation of reactive oxygen species (ROS), cyclooxygenase products, or cysteinyl leukotrienes (LTs). Addition of FMLP alone did not increase microvascular permeability (Kf). When PMNs were added to the isolated lung, FMLP caused an 80% increase in Kf. Wet-to-dry weight ratio was also significantly increased with PMNs + FMLP compared with FMLP only. There was a significant positive correlation between total myeloperoxidase activity in lung tissue and Kf values after FMLP (30 min). Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate or ibuprofen, had no effect on the PMN + FMLP-induced increase in Kf. However, the ROS inhibitor catalase and the nonantioxidant LT synthesis blocker MK 886 inhibited the PMN + FMLP increase in Kf. Perfusate levels of LTs (LTC4, -D4, and -E4) were significantly increased from baseline values 30 min after FMLP. Both MK 886 and catalase suppressed the elevation of LTs after PMN + FMLP. These results indicate that FMLP increased a pulmonary microvascular permeability in isolated buffer-perfused rabbit lungs that is PMN dependent and mediated by LT produced possibly by a result of ROS production.

Bronchoalveolar eosinophilia in random-source versus purpose-bred dogs.

Eosinophils (EOS) have been implicated in changes in airway and vascular reactivity in a variety of disease states. Analysis of cells in bronchoalveolar lavage samples from chronic, heartworm-free random-source (RS) dogs indicated higher leukocyte counts with markedly higher percent and total numbers of EOS than were present in purpose-bred (PB) animals. Bronchoalveolar lavage fluid (BALF) obtained from RS dogs had a significantly elevated total nucleated cell count: 0.8 x 10(6) vs 0.4 x 10(6) for the PB dogs. RS dogs had 24% +/- 5% and PB dogs had 3% +/- 0.7% EOS. The RS animals with elevated EOS had similar percentages of neutrophils: 4% +/- 0.6% as the PB animals. Despite aggressive anthelminthic treatment, the abnormal BALF cellular profile of the RS animals persisted even though circulating levels of EOS in this group decreased. Analysis of BALF for thromboxane B2 (TxB2) and 6-keto-prostaglandin F1(1a) (6-keto-PGF1a) indicated that only the TxB2 levels were significantly different between groups. The RS BALF TxB2 levels were 73 +/- 14 pg/ml vs 23 +/- 3 pg/ml for the PB group (P < 0.05). Regression analysis of the relationship between increasing TxB2 levels and the absolute number of EOS per milliliter of BALF obtained from the RS dogs indicated a significant correlation (r = 0.83, P < 0.0001). No difference in plasma levels of these mediators was observed. Other physiologic parameters also differed between the two groups: the RS group had significantly increased heart rates and cardiac output under baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of two epidural alpha 2-agonists, guanfacine and clonidine, in regard to duration of antinociception, and ventilatory and hemodynamic effects in goats.

Epidural clonidine produces analgesia in humans with acute and chronic pain. Its use is limited because of short-lasting analgesia, hemodynamic depression, sedation, and respiratory depression. Intrathecal guanfacine has a longer duration of action than intrathecal clonidine. The present study compares these two drugs administered epidurally. Pulmonary artery, carotid artery, and epidural catheters were inserted into five goats. Each animal received guanfacine 5 mg/10 mL, clonidine 750 micrograms/10 mL, or a 10-mL saline control solution on separate occasions. Antinociception (tested via a point pressure stimulation device), arterial blood pressure, heart rate, cardiac output, pulmonary capillary wedge pressure, and arterial and mixed venous blood gases were measured every 30 min for 8 h. Guanfacine produced a longer duration of antinociception (guanfacine = 8 h vs clonidine = 5.5 h). Increases in PaCO2 were more pronounced in the clonidine group. There were no marked hemodynamic differences between the two drugs. Pretreatment with epidural idazoxan, an alpha 2-antagonist, blocked the antinociceptive effects of guanfacine. Because of a longer duration of action and less respiratory depression, epidural guanfacine may be superior for postoperative analgesia and chronic pain syndromes.

Rapid separation of creatine, phosphocreatine and adenosine metabolites by ion-pair reversed-phase high-performance liquid chromatography in plasma and cardiac tissue.

A rapid ion-pair reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous detection of creatine, phosphocreatine, hypoxanthine, inosine, adenosine, AMP, ADP, ATP, 8-azaguanine, 2-chloroadenosine, and 2'-O-methyladenosine. This method has proven useful for measuring changes in nucleotide concentrations in both heart tissue and plasma samples. Separation of the compounds of interest is achieved in less than 8 min with re-equilibration in 7 min, making the total run time 15 min. Separation is performed on a 3-microns Ultrasphere ODS column employing tetrabutylammonium phosphate as the ion-pair agent and dipotassium hydrogenphosphate as the counter ion. The accuracy, rapid separation, and re-equilibration time make this method particularly useful for the routine analysis of a large number of samples.

Mechanisms of pulmonary vasoconstriction induced by chemotactic peptide FMLP in isolated rabbit lungs.

The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been shown to constrict both bronchial and coronary vascular smooth muscle through the action of cyclooxygenase or lipoxygenase products. We observed that intravenous FMLP increased pulmonary vascular resistance (PVR) in isolated buffer-perfused rabbit lungs. FMLP increased the PVR (primarily in the middle segment of the pulmonary vascular bed) at concentrations greater than or equal to 10(-7) M. Maximum vasoconstriction occurred at 5 min and then slowly declined to a level that remained above baseline at 30 min. Tachyphylaxis was observed in response to FMLP. When polymorphonuclear leukocytes (PMNs) were added to the perfusate, FMLP caused a greater increase in PVR. PMN depletion with dimethylmyleran significantly reduced the PVR response to FMLP. Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate and ibuprofen, and the leukotriene synthesis blocker MK 886 had no effect on the FMLP-induced vasoconstriction. However, the reactive oxygen species scavenger catalase significantly reduced the vasoconstriction. These results suggest that FMLP induces vasoconstriction that is dependent on PMNs and mediated by reactive oxygen species with no involvement of cyclooxygenase or lipoxygenase products.

Ibuprofen reduces ethchlorvynol lung injury: possible role of blood flow distribution.

The role of cyclooxygenase products in acute lung injury was determined by pretreatment of dogs with ibuprofen before injury with intravenous ethchlovynol (ECV). In animals given ECV only, lung injury resulted in extravascular lung water of 18.9 ml/kg after 2 h, which was significantly higher than the 14.8 ml/kg in the group pretreated with ibuprofen. The comparison of gravimetric and indicator-dilution measurements of edema fluid indicates that edema fluid could not be reliably detected after treatment with ibuprofen because of diversion of flow from injured areas. Venous admixture increased from 6% at baseline to 32% 120 min after ECV in the vehicle-pretreated group compared with an increase from 4% at baseline to 7% in the ibuprofen-pretreated group. The regression analysis of the relationship between venous admixture and extravascular lung water indicated that, at any level of edema, venous admixture was significantly less in the group treated with ibuprofen than in the untreated group. Measurement of plasma and bronchoalveolar lavage fluid indicated that ibuprofen inhibited cyclooxygenase activity without affecting lipoxygenase activity. These results suggest that in intact dogs ibuprofen has a protective effect on both pulmonary gas transfer and pulmonary edema formation in ECV-injured lungs, which is consistent with limiting blood flow to injured segments of the lung.

Hypercarbia during carbon dioxide pneumoperitoneum.

Patients with cardiopulmonary insufficiency undergoing laparoscopic surgery with carbon dioxide (CO2) pneumoperitoneum may retain CO2 resulting in clinically significant respiratory acidosis. A canine model of pulmonary emphysema induced by papain inhalation was utilized to evaluate the respiratory effects of both CO2 and helium pneumoperitoneum. Prior to papain inhalation and 5 and 8 weeks after initial treatment under general anesthesia, mechanical ventilation was adjusted to maintain the end-tidal CO2 (ETCO2) at 40 mm Hg during baseline and pneumoperitoneum physiologic monitoring periods. Utilizing an analysis of variance, hemodynamic and respiratory physiologic parameters were compared. In this canine model, all dogs demonstrated consistent hypercarbia during CO2 pneumoperitoneum prior to papain treatments, but CO2 retention was significantly increased in the emphysematous state. The occurrence of hypercarbia during CO2 pneumoperitoneum may be underestimated by ETCO2 monitoring as was revealed by an increased PaCO2 (arterial carbon dioxide pressure)-ETCO2 gradient with an increasing time interval between papain exposure and period of physiologic monitoring. Irrespective of the pulmonary condition of the dog, helium pneumoperitoneum did not produce any hypercarbic or acidic changes when compared with the concomitant baseline period of dogs prior to the induction of pneumoperitoneum, thus suggesting that helium pneumoperitoneum may be a reasonable alternative in patients at risk for CO2 retention.

Adenosine prevents phorbol ester injury in rabbit lungs: role of leukotrienes and TNF.

The objective of this study was to determine whether adenosine (ADO) prevents phorbol myristate acetate- (PMA) induced lung injury by modulating peptidoleukotrienes (LT) and/or tumor necrosis factor (TNF) production. PMA significantly increased pulmonary vascular resistance (PVR, 275 +/- 4 to 447 +/- 30 cmH2O.1-1.min) and microvascular filtration coefficient.(Kf, 0.024 +/- 0.002 to 0.040 +/- 0.006 g.min-1.cmH2O-1) in isolated blood-perfused rabbit lungs. ADO (5 mumol/min) blocked the increases in PVR (257 +/- 9 to 283 +/- 26) and Kf (0.028 +/- 0.005 to 0.018 +/- 0.002). After PMA (30 min), perfusate levels of LTC4 + LTD4 increased by 15.3 +/- 2.1 pg/ml; LTE4 increased by 15.1 +/- 4.1 pg/ml. ADO reduced the increase in LTC4 + LTD4 to 2.7 +/- 6.1 pg/ml, but total LT increased by 31.9 +/- 16.6 pg/ml, implying that ADO enhanced the conversion of LTC4 and LTD4 to LTE4. MK-886 (L663,536), an LT synthesis inhibitor, blocked the increase in total LT (6.1 +/- 13.9 pg/ml) but did not reduce the PMA-induced increase in Kf (0.022 +/- 0.003 to 0.035 +/- 0.005) or PVR (238 +/- 11 to 495 +/- 21). After PMA administration, perfusate TNF levels were not different from the 10-fold increase observed in control experiments and were not reduced by ADO or MK-886. TNF production was independent of perfusate blood components and presumably due to low levels of endotoxin in the perfusate (70-90 ng/ml). These results indicate that ADO does not protect against PMA-induced acute lung injury by altering circulating levels of LT or TNF.

Analysis of the hemodynamic and ventilatory effects of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy uses carbon dioxide, a highly diffusable gas, for insufflation. With extended periods of insufflation, patient arterial carbon dioxide levels may be adversely altered. Patients were selected for laparoscopic cholecystectomy using the same criteria as for open cholecystectomy. Twenty patients (group 1) had normal preoperative cardiopulmonary status (American Society of Anesthesiologists class I), while 10 patients (group 2) had previously diagnosed cardiac or pulmonary disease (class II or III). Demographic, hemodynamic, arterial blood gas, and ventilatory data were collected before peritoneal insufflation and at intervals during surgery. Patients with preoperative cardiopulmonary disease demonstrated significant increases in arterial carbon dioxide levels and decreases in pH during carbon dioxide insufflation compared with patients without underlying disease. Results of concurrent noninvasive methods of assessing changes in partial arterial pressures of carbon dioxide (end-tidal carbon dioxide measured with mass spectrographic techniques) may be misleading and misinterpreted because changes in partial arterial pressures of carbon dioxide are typically much smaller than changes in arterial blood levels and, unlike arterial gas measurements, do not indicate the true level of arterial hypercarbia. During laparoscopic cholecystectomy, patients with chronic cardiopulmonary disease may require careful intraoperative arterial blood gas monitoring of absorbed carbon dioxide.

Cyclooxygenase inhibition prevents PMA-induced increases in lung vascular permeability.

The effect of cyclooxygenase inhibition in phorbol myristate acetate (PMA)-induced acute lung injury was studied in isolated constant-flow blood-perfused rabbit lungs. PMA caused a 51% increase in pulmonary arterial pressure (localized in the arterial and middle segments as measured by vascular occlusion pressures), a 71% increase in microvascular permeability (measured by the microvascular fluid filtration coefficient, Kf), and a nearly threefold increase in perfusate thromboxane (Tx) B2 levels. Cyclooxygenase inhibition with three chemically dissimilar inhibitors, indomethacin (10(-7) and 10(-6) M), meclofenamate (10(-6) M), and ibuprofen (10(-5) M), prevented the Kf increase without affecting the pulmonary arterial pressure increase or resistance distribution changes after PMA administration. The specific role of TxA2 was investigated by pretreatment with OKY-046, a specific Tx synthase inhibitor, or infusion of SQ 29548, a TxA2 receptor antagonist; both compounds failed to protect against either the PMA-induced permeability or the vascular resistance increase. These results indicate that cyclooxygenase-mediated products of arachidonic acid other than TxA2 mediate the PMA-induced permeability increase but not the hypertension.

Evaluation of extravascular lung water by single thermal indicator.

Much attention has been directed to developing early therapy that might prevent or ameliorate incipient adult respiratory distress syndrome (ARDS) before respiratory failure ensues. The relationship between increased extravascular lung water (EVLW) and pulmonary microvascular pressure has been used by numerous investigators to confirm alterations in the permeability of the alveolar capillary membrane. In the present study, EVLW was measured in 40 critically ill patients by an indicator dilution technique utilizing thermal indicator alone. Injection of cold saline distinguished intravascular and extravascular compartments with a sensitivity similar to that of the thermal-dye double-indicator dilution technique but without the withdrawal of blood, dye densitometry, or the preparation of special injectate. Both absolute volumes and volume changes over time measured by the single thermal indicator method compared favorably (p less than .001) to EVLW values determined simultaneously by the conventional thermal-dye double-indicator dilution technique. These results suggest that the single thermal indicator technique may help identify the earliest phase of ARDS when fluid is starting to accumulate in the lung interstitium.

Cytoplasmic oestrogen receptor replenishment: oestrogens versus anti-oestrogens.

The effect of the in vivo administration of various triphenylethylene antioestrogens and physiological (0.05 microgram) versus pharmacological (0.5--5 microgram) doses of oestradiol-17 beta (Oe2) on the uterotrophic process in general and the nuclear accumulation and cytoplasmic depletion and replenishment of uterine oestrogen receptor was determined. Regardless of the dose of Oe2 the changes in uterine wet weight, total protein and incorporation of [3H]thymidine into DNA and [14C]leucine into protein were the same at 24 h. The anti-oestrogen receptor was also studied. The net increase, above control, of cytoplasmic oestrogen receptor at 24 h and 48 h after Oe2 injection was approximately 0.35 and 0.77 pmoles/uterus, respectively. The effect of anti-oestrogens (U-11,100A, CI628, en- and zuclomiphene) on the increase in cytoplasmic oestrogen receptor at 24 h and 48 h measured from maximally depleted levels was nearly identical to the Oe2 induced net increase. This suggests that in both cases these particular increases represent newly synthesized receptor and that Oe2 causes some receptor replenishment through a recycling process.

Different nuclear binding sites for antiestrogen and estrogen receptor complexes.

Experiments were performed to determine the in vivo effect of various estrogens and anti-estrogens on the nuclear accumulation and retention of estrogen receptors, the cytoplasmic levels of estrogen receptors, and the formation of salt-resistant and salt-extractable forms of the nuclear estrogen receptor in immature rat uteri. A 5 mug injection of estradiol-17beta (E2) or diethylstilbestrol (DES) resulted in a maximal nuclear translocation of the receptor complexes by 1 h with a subsequent rapid decrease of both the estradiol receptor complex (ERC) and diethylstilbestrol receptor complex (DRC) to levels found in uteri of saline-injected rats by 12 h. However, the antiestrogens U-11,100A, zuclomiphene and enclomphene (100 mug/injection) resulted in a slower nuclear accumulation of receptor complex which continued to increase through 24 h. The cytosol receptor levels with E2 and DES were depleted to 10--20% of control levels within 1 h, but then were replenished so that they were above control levels by 24 h. The clomiphene-type compounds also showed an initial depletion of cytosol estrogen receptor, but the antiestrogens were almost ineffective in receptor replenishment. The estrogen receptor translocated to the nuclear fraction by estrogens demonstrated both salt-extractable (0.3M KCl) and salt-resistant forms at 1--6 h, whereas the clomiphene-type compounds resulted in the formation of only a salt-extractable form of the estrogen receptor at all times. By 12--24 h after injection, the salt-resistant forms of the ERC and DRC were no longer present. The effect of varying the dosage of injected E2 (0.05 mug-5 mug) resulted in the formation of an identical amount of salt-resistant ERC at 1--2 h, whereas the total amount of nuclear ERC (salt-resistant and salt-extractable) varied with the injected dose of E2. However, at 6 h, the amount of salt resistant ERC varied with the injected dose of E2 (0.005-5 mug). These results suggest that the nuclear salt-resistant form (formed by estrogens only) of the estrogen receptor is required for true uterine growth, whereas the nuclear salt-extractable form may be only sufficient for short term estrogenic responses.