Ann Otol 85: 1976
TRACHEAL RESECTION AND MUCOCILIARY CLEARANCE ANTHONY GIORDANO,
MD
MINNEAPOLIS, MINNESOTA
DOUGLAS
S.
HOLSCLAW,
MD
PHILADELPHIA, PENNSYLVANIA
SUMMARY - Mucociliary transport following tracheal resection and end-to-end anastomosis was evaluated in beagle dogs, using the movement of 99~lTC labeled sodium pertechnetate solution as a marker. Preoperatively, mucociliary clearance was stable, but a three-fold decrease in tracheal mucus movement was found three days postoperatively. Clearance rates had returned to normal by 31 days postoperatively and remained stable over a ten week period of observation. By histological examination, normal ciliated epithelium was seen within six months following resection and anastomosis. Since up to 25% (4 em or seven tracheal rings) of tracheal length was removed, significant longitudinal loss can take place without functional impairment of mucociliary clearance. Circumferential narrowing, however, was associated with a significant decrease in clearance.
Tracheal stenosis and its repair have been reported in the literature for the nast 100 years.' Many methods have been utilized in the repair of tracheal stenosis, including circumferential resection with primary anastomosis.v" endoscopic resection.s-? and resection with the use of a prosthesis.s!' Circumferential resection with primary anastomosis has become the most effective corrective procedure in most cases of tracheal stenosis. 2-5,12-l5 The first successful resection and anastomosis was performed by Kuester in 1884. 1 Other investigators at the tum of the century reported successful resections and anastomoses of segments up to 4 em.' More recently, investigators have reported that one of the limiting factors in determining success or failure was the tension at the suture line. l,9,12,13 In dogs, primary anastomosis is 100% successful provided the suture line tension is below 1700 gm. l,13 In humans, defects requiring more than 30% resection (3-4 cm) can be repaired end-to-end only after a procedure to decrease suture line
tension, such as extreme neck f1.exion,2,15-IS substernal methods of pulmonary freeing,2,5,12,15-19 or laryngeal release 20-22 is performed. These methods either alone or in combination have made possible resections in humans of up to 7 cm (ten tracheal rings). Resection with primary anastomosis restores the lumen of the trachea to an anatomically acceptable caliber. However, effects of the procedure on the more subtle aspects of tracheal function such as mucociliary clearance are unknown. Mucostasis has long been thought to predispose to tracheobronchial infections. The trauma and anatomical break in the tracheal mucosa postanastomosis may cause a slowing of the mucus clearance with a resultant accumulation of secretions and increased possibility of infection. These, in tum, may hinder healing at the anastomotic site. Thus it is desirous to have information about the return of mucociliary clearance after the surgical procedure.
From the Department of Pediatrics, Section of Pediatric Pulmonary Disease, Hahnemann Medical College and Hospital, Philadelphia; and Department of Radiation Biology and Biophysics, University of Rochester, New York. Supported by NIH Research grant AM-I7771 and Pulmonary Academic Award No. K07-HL-70832 (DSH). Presented at the meeting of the American Broncho-Esophagological Association, Palm Beach, Florida, April 27-28, 1976. 631
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 11, 2015
632
GIORDANO-HOLSCLAW
Fig. 1. Typical chart recordings. Top tracings on each of the sets are from cephalad detector, bottom tracings are from caudal detector. FET - First edge time.
We have studied the effects on tracheal mucociliary clearance of tracheal resection with subsequent end-to-end anastomosis at clinically acceptable suture line tensions. Histologic studies of the anastomotic sites were used to monitor the return of normal tracheal epithelium and to relate these observations to the physiologic function of mucociliary clearance. METHODS AND MATERIALS
Two groups of dogs were studied. Group A. Five conditioned adult mongrel dogs (6-10 kg) underwent tracheal resection and primary anastomosis. These dogs were sacrificed four to six months postoperatively, and the anastomotic site removed for gross and histological evaluation. Group B. Seven adult purebred female beagles (6-10 kg), of whom six were subjected to preoperative tracheal mucus clearance measurements, underwent tracheal re-
section and primary anastomosis. Clearance measurements were repeated on the third postoperative day, and then repeated every two weeks for ten weeks. Two of these dogs also underwent bronchoscopy and tracheography. The remaining dog was the unoperated control and had only mucus clearance studies performed. Surgical Procedure. The technique employed was similar to that reported by Wardell et al.23 Intravenous pentobarbital sodium (40-50 mg/ kg) was used for anesthesia. The ventral neck area was aseptically prepared, and a midline cervical incision made from just anterior to the cricoid cartilage to the suprasternal notch. The trachea was exposed from the cricoid cartilage to the 14th ring (7-10 cm) and the nerves and blood vessels blunt dissected at the areas where the trachea was to be transected. Medial 000 silk sutures were placed at the transection sites. Lateral 000 silk sutures were placed between rings 4 and either 13 or 14. The trachea was then transected first below the lIth or 12th ring caudad and then just below the fifth ring cephalad. The transected tracheal piece was moved to the
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 11, 2015
TRACHEAL MUCOCILIARY CLEARANCE
633
Fig. 2. Tracheal section. Arrow indicates malalignment of cartilaginous rings at what is thought to be the anastomotic site. Note proper alignment of cartilaginous rings to the left. (X20) s.de, and the lateral silk retention sutures were tightened to bring the tracheal ends within 2 em of each other. Ten to 14 interrupted 000 chromic sutures on an atraumatic needle were used for the anastomosis, entrapping one cartilaginous ring from each end. All knots were outside the lumen. The transected section of six to seven rings was allowed to remain beside the intact trachea. This was done to insure continuity of the vasculature below and innervation above the transection site, as well as allow a tracheal pouch to be formed for mucus collections involved in a separate study. A continuous locked 00 chromic suture was used to approximate the sternohyoid muscles in the midline. Then 4-000 interrupted chromic sutures were placed on each side to tack the subcutaneous tissues to the sternohyoid and sternothyroid muscles. Twelve to 16 00 silk double mattress sutures were used to close the skin. The dog was allowed glucose in water until the first postoperative clearance measurement was made on postoperative day three. Clearance. Clearance was measured in the supine pentothal anesthetized dog by a previously described radioisotope method. 24 Five 1'1 of a 99MTC labeled Na-pertechnetate solution, a y emitter, was injected into a percutaneous tracheal pilot needle.. Three cubic centimeters of air were then blown through the injection needle depositing the isotope on the tracheal mucosa. The movement of the pertechnetate solution from one 3 mm cross section of trachea to another section 35 mm more cephalad was the marker for mucociliary transport. This movement was followed by two
NaI crystal scintillation detectors" connected to count rate meters"" and chart recorders""" which provided the records from which mucus transport times and velocities were determined. Transport time was expressed as a "First Edge Time" (FET), which was the time interval for the mucus to move 35 mm. Rectal temperatures ranged between 37-39 C and only one clearance measurement per dog was made on a test day. Figure 1 shows typical tracings recorded at various pre- and postoperative times. RESULTS
Group A. All dogs survived the resection and anastomosis. None showed signs of upper airway distress or obstruction. At sacrifice four to six months postoperatively, all five dogs showed cervical tracheal adhesions. On gross inspection of both the external and luminal tracheal surfaces, it was difficult to determine the anastomotic site. Only one dog had noticeable intratracheal stenosis. This was confined mainly to the posterior wall and caused less than a 20% reduction in tracheal cross-sectional area. On histologic inspection, slight malalignment of the cartilaginous rings aided in localizing the anastomotic site (Fig. 2). The mucosa itself gave no indication of the transection. In some anastomotic areas, the mucosa was
" No. 6S4/1.5 "Integral Line Assembly." Harshaw Chemical Co Solon OH "" Nuclear Chicago 1620. Searle Analytic, Inc, Des Plaines, IL.' , . """ Sanborn Twin-Visa 60-1300. Sanborn Co, Cambridge, MA.
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 11, 2015
634
GIORDANO-HOLSCLAW
. . Fig. 3. A) Nor~al. trach~a. Uniformity of epithelial layer is outstanding characterB) Anastomotic site. Disorganization and increased thickness of epithelial la er IS present. (X800 ) y ~stlc.
thicker, and the basal layer more disorganized but the ciliated outer layer was continuous, making it difficult to distinguish normal from anastomotic mucosa (Figs. 3, 4). G:r~up B. T~e control dog (No.7) exhibited a consistent mucociliary clearance pattern throughout the entire study (Table I). The FET over the four-month period was 284±36 sec (mean ± Standard Deviation of Mean) and the clearance velocity 7.5±1.1 rum/min.
From 31 days on, as a group, the FET was 235±135 sec and clearance velocity 10.4±3.1 mrn/min, Three of the dogs had postoperative clearance rates which increa~ed 19, 41 and 86% over their preoperative measurements. The other three had rates which decreased 7 16 a.nd 3S% from their respective preop~ra tive values. Once baseline preoperative clearance rates were reached postoperati~e.ly, all ?o~s except one (No.6) exhibited a similar degree of internal consiste~c.y as they had in the preoperative condition,
In the preoperative dogs, mucociliary clearance was also found to be relatively stable. The variations in individual clearance velocities and times for anyone dog were less than the variations in measurements between two dogs. Thus, each dog was used as its own control. The FET was 231±80 sec and the clearance velocity 1O.1±3.2 mm /min preoperatively. All dogs survived the surgery and had six postoperative clearance studies. Three days after surgery there was a three-fold or greater decrease in mucociliary clearance when compared to the slowest preoperative measurement (p < .02). Within 31 days, clearance returned to normal preoperative levels in all dogs.
Approximately two months postoperative, the clearance rates of one of the dogs (No.6) began to decrease. Two measurements over the next month indicated that the mucociliary clearance which had apparently returned to normal within 31 days was now depressed to only 30-40% of normal. Also, this dog had a wheeze when excited. It was felt that possible stenosis at the anastomotic site was responsible. Bronchoscopy and tracheography were performed on this do~ as. well as on a dog (No.1) who maintained normal clearance function during the 2~f month postoperative period. Bronchoscopy in both dogs revealed
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 11, 2015
635
TRACHEAL MUCOCILIARY CLEARANCE TABLE I PRE- AND POSTOPERATIVE FIRST EDGE TIME AND VELOCITY STUDIES
Preoperative day
Dog 1 2 3 4 5 6"
49 220 190 180 310 220 200
7""" 210
1 2 3 4 5 6 7
35 280 160 180 380 310 120
21 210
7 180 170 200 350 250
140 2.'30 410 350 170 150 Average"? 330 280 310
9.2 7.5 10.0 11.7 ILl 13.1 15.0 12.4 11.7 11.7 9.1 10.5 6.8 5.5 5.2 6.0 9.2 6.8 6.0 8.4 10.5 17..5 12.4 14.0 Average 10.0 6.4 7.5 6.8
Postoperative day Mean> First time edge in seconds S.D. 17 31 3 222±42 >750 280 160 165±21 >600 150 150 197±24 >750 460 200 362±43 >1800 260 170 282±59 >1050 300 160 160±34 >600 250 180 231±80 170±18 282±53 280 300 310 Velocity 9.6±1.7 12.9±1.6 1O.8±1.2 5.9±0.7 7.6±1.5 13.6±3.0 10.1±3.2 7.7±1.6
Mean-t
45
59
240 200 340 210
160 250 200 160
210 140
73 200 140
S.D.'''''' " 190±38
230 250
185±51 242±67 198±41
190 600
250
202±38
660
250
310
260
393±273 235±130 282±32
10.5 15.0
in mm/min.
TRACHEAL RESECTION AND MUCOCILIARY CLEARANCE ANTHONY GIORDANO,
MD
MINNEAPOLIS, MINNESOTA
DOUGLAS
S.
HOLSCLAW,
MD
PHILADELPHIA, PENNSYLVANIA
SUMMARY - Mucociliary transport following tracheal resection and end-to-end anastomosis was evaluated in beagle dogs, using the movement of 99~lTC labeled sodium pertechnetate solution as a marker. Preoperatively, mucociliary clearance was stable, but a three-fold decrease in tracheal mucus movement was found three days postoperatively. Clearance rates had returned to normal by 31 days postoperatively and remained stable over a ten week period of observation. By histological examination, normal ciliated epithelium was seen within six months following resection and anastomosis. Since up to 25% (4 em or seven tracheal rings) of tracheal length was removed, significant longitudinal loss can take place without functional impairment of mucociliary clearance. Circumferential narrowing, however, was associated with a significant decrease in clearance.
Tracheal stenosis and its repair have been reported in the literature for the nast 100 years.' Many methods have been utilized in the repair of tracheal stenosis, including circumferential resection with primary anastomosis.v" endoscopic resection.s-? and resection with the use of a prosthesis.s!' Circumferential resection with primary anastomosis has become the most effective corrective procedure in most cases of tracheal stenosis. 2-5,12-l5 The first successful resection and anastomosis was performed by Kuester in 1884. 1 Other investigators at the tum of the century reported successful resections and anastomoses of segments up to 4 em.' More recently, investigators have reported that one of the limiting factors in determining success or failure was the tension at the suture line. l,9,12,13 In dogs, primary anastomosis is 100% successful provided the suture line tension is below 1700 gm. l,13 In humans, defects requiring more than 30% resection (3-4 cm) can be repaired end-to-end only after a procedure to decrease suture line
tension, such as extreme neck f1.exion,2,15-IS substernal methods of pulmonary freeing,2,5,12,15-19 or laryngeal release 20-22 is performed. These methods either alone or in combination have made possible resections in humans of up to 7 cm (ten tracheal rings). Resection with primary anastomosis restores the lumen of the trachea to an anatomically acceptable caliber. However, effects of the procedure on the more subtle aspects of tracheal function such as mucociliary clearance are unknown. Mucostasis has long been thought to predispose to tracheobronchial infections. The trauma and anatomical break in the tracheal mucosa postanastomosis may cause a slowing of the mucus clearance with a resultant accumulation of secretions and increased possibility of infection. These, in tum, may hinder healing at the anastomotic site. Thus it is desirous to have information about the return of mucociliary clearance after the surgical procedure.
From the Department of Pediatrics, Section of Pediatric Pulmonary Disease, Hahnemann Medical College and Hospital, Philadelphia; and Department of Radiation Biology and Biophysics, University of Rochester, New York. Supported by NIH Research grant AM-I7771 and Pulmonary Academic Award No. K07-HL-70832 (DSH). Presented at the meeting of the American Broncho-Esophagological Association, Palm Beach, Florida, April 27-28, 1976. 631
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 11, 2015
632
GIORDANO-HOLSCLAW
Fig. 1. Typical chart recordings. Top tracings on each of the sets are from cephalad detector, bottom tracings are from caudal detector. FET - First edge time.
We have studied the effects on tracheal mucociliary clearance of tracheal resection with subsequent end-to-end anastomosis at clinically acceptable suture line tensions. Histologic studies of the anastomotic sites were used to monitor the return of normal tracheal epithelium and to relate these observations to the physiologic function of mucociliary clearance. METHODS AND MATERIALS
Two groups of dogs were studied. Group A. Five conditioned adult mongrel dogs (6-10 kg) underwent tracheal resection and primary anastomosis. These dogs were sacrificed four to six months postoperatively, and the anastomotic site removed for gross and histological evaluation. Group B. Seven adult purebred female beagles (6-10 kg), of whom six were subjected to preoperative tracheal mucus clearance measurements, underwent tracheal re-
section and primary anastomosis. Clearance measurements were repeated on the third postoperative day, and then repeated every two weeks for ten weeks. Two of these dogs also underwent bronchoscopy and tracheography. The remaining dog was the unoperated control and had only mucus clearance studies performed. Surgical Procedure. The technique employed was similar to that reported by Wardell et al.23 Intravenous pentobarbital sodium (40-50 mg/ kg) was used for anesthesia. The ventral neck area was aseptically prepared, and a midline cervical incision made from just anterior to the cricoid cartilage to the suprasternal notch. The trachea was exposed from the cricoid cartilage to the 14th ring (7-10 cm) and the nerves and blood vessels blunt dissected at the areas where the trachea was to be transected. Medial 000 silk sutures were placed at the transection sites. Lateral 000 silk sutures were placed between rings 4 and either 13 or 14. The trachea was then transected first below the lIth or 12th ring caudad and then just below the fifth ring cephalad. The transected tracheal piece was moved to the
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 11, 2015
TRACHEAL MUCOCILIARY CLEARANCE
633
Fig. 2. Tracheal section. Arrow indicates malalignment of cartilaginous rings at what is thought to be the anastomotic site. Note proper alignment of cartilaginous rings to the left. (X20) s.de, and the lateral silk retention sutures were tightened to bring the tracheal ends within 2 em of each other. Ten to 14 interrupted 000 chromic sutures on an atraumatic needle were used for the anastomosis, entrapping one cartilaginous ring from each end. All knots were outside the lumen. The transected section of six to seven rings was allowed to remain beside the intact trachea. This was done to insure continuity of the vasculature below and innervation above the transection site, as well as allow a tracheal pouch to be formed for mucus collections involved in a separate study. A continuous locked 00 chromic suture was used to approximate the sternohyoid muscles in the midline. Then 4-000 interrupted chromic sutures were placed on each side to tack the subcutaneous tissues to the sternohyoid and sternothyroid muscles. Twelve to 16 00 silk double mattress sutures were used to close the skin. The dog was allowed glucose in water until the first postoperative clearance measurement was made on postoperative day three. Clearance. Clearance was measured in the supine pentothal anesthetized dog by a previously described radioisotope method. 24 Five 1'1 of a 99MTC labeled Na-pertechnetate solution, a y emitter, was injected into a percutaneous tracheal pilot needle.. Three cubic centimeters of air were then blown through the injection needle depositing the isotope on the tracheal mucosa. The movement of the pertechnetate solution from one 3 mm cross section of trachea to another section 35 mm more cephalad was the marker for mucociliary transport. This movement was followed by two
NaI crystal scintillation detectors" connected to count rate meters"" and chart recorders""" which provided the records from which mucus transport times and velocities were determined. Transport time was expressed as a "First Edge Time" (FET), which was the time interval for the mucus to move 35 mm. Rectal temperatures ranged between 37-39 C and only one clearance measurement per dog was made on a test day. Figure 1 shows typical tracings recorded at various pre- and postoperative times. RESULTS
Group A. All dogs survived the resection and anastomosis. None showed signs of upper airway distress or obstruction. At sacrifice four to six months postoperatively, all five dogs showed cervical tracheal adhesions. On gross inspection of both the external and luminal tracheal surfaces, it was difficult to determine the anastomotic site. Only one dog had noticeable intratracheal stenosis. This was confined mainly to the posterior wall and caused less than a 20% reduction in tracheal cross-sectional area. On histologic inspection, slight malalignment of the cartilaginous rings aided in localizing the anastomotic site (Fig. 2). The mucosa itself gave no indication of the transection. In some anastomotic areas, the mucosa was
" No. 6S4/1.5 "Integral Line Assembly." Harshaw Chemical Co Solon OH "" Nuclear Chicago 1620. Searle Analytic, Inc, Des Plaines, IL.' , . """ Sanborn Twin-Visa 60-1300. Sanborn Co, Cambridge, MA.
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 11, 2015
634
GIORDANO-HOLSCLAW
. . Fig. 3. A) Nor~al. trach~a. Uniformity of epithelial layer is outstanding characterB) Anastomotic site. Disorganization and increased thickness of epithelial la er IS present. (X800 ) y ~stlc.
thicker, and the basal layer more disorganized but the ciliated outer layer was continuous, making it difficult to distinguish normal from anastomotic mucosa (Figs. 3, 4). G:r~up B. T~e control dog (No.7) exhibited a consistent mucociliary clearance pattern throughout the entire study (Table I). The FET over the four-month period was 284±36 sec (mean ± Standard Deviation of Mean) and the clearance velocity 7.5±1.1 rum/min.
From 31 days on, as a group, the FET was 235±135 sec and clearance velocity 10.4±3.1 mrn/min, Three of the dogs had postoperative clearance rates which increa~ed 19, 41 and 86% over their preoperative measurements. The other three had rates which decreased 7 16 a.nd 3S% from their respective preop~ra tive values. Once baseline preoperative clearance rates were reached postoperati~e.ly, all ?o~s except one (No.6) exhibited a similar degree of internal consiste~c.y as they had in the preoperative condition,
In the preoperative dogs, mucociliary clearance was also found to be relatively stable. The variations in individual clearance velocities and times for anyone dog were less than the variations in measurements between two dogs. Thus, each dog was used as its own control. The FET was 231±80 sec and the clearance velocity 1O.1±3.2 mm /min preoperatively. All dogs survived the surgery and had six postoperative clearance studies. Three days after surgery there was a three-fold or greater decrease in mucociliary clearance when compared to the slowest preoperative measurement (p < .02). Within 31 days, clearance returned to normal preoperative levels in all dogs.
Approximately two months postoperative, the clearance rates of one of the dogs (No.6) began to decrease. Two measurements over the next month indicated that the mucociliary clearance which had apparently returned to normal within 31 days was now depressed to only 30-40% of normal. Also, this dog had a wheeze when excited. It was felt that possible stenosis at the anastomotic site was responsible. Bronchoscopy and tracheography were performed on this do~ as. well as on a dog (No.1) who maintained normal clearance function during the 2~f month postoperative period. Bronchoscopy in both dogs revealed
Downloaded from aor.sagepub.com at FLORIDA ATLANTIC UNIV on July 11, 2015
635
TRACHEAL MUCOCILIARY CLEARANCE TABLE I PRE- AND POSTOPERATIVE FIRST EDGE TIME AND VELOCITY STUDIES
Preoperative day
Dog 1 2 3 4 5 6"
49 220 190 180 310 220 200
7""" 210
1 2 3 4 5 6 7
35 280 160 180 380 310 120
21 210
7 180 170 200 350 250
140 2.'30 410 350 170 150 Average"? 330 280 310
9.2 7.5 10.0 11.7 ILl 13.1 15.0 12.4 11.7 11.7 9.1 10.5 6.8 5.5 5.2 6.0 9.2 6.8 6.0 8.4 10.5 17..5 12.4 14.0 Average 10.0 6.4 7.5 6.8
Postoperative day Mean> First time edge in seconds S.D. 17 31 3 222±42 >750 280 160 165±21 >600 150 150 197±24 >750 460 200 362±43 >1800 260 170 282±59 >1050 300 160 160±34 >600 250 180 231±80 170±18 282±53 280 300 310 Velocity 9.6±1.7 12.9±1.6 1O.8±1.2 5.9±0.7 7.6±1.5 13.6±3.0 10.1±3.2 7.7±1.6
Mean-t
45
59
240 200 340 210
160 250 200 160
210 140
73 200 140
S.D.'''''' " 190±38
230 250
185±51 242±67 198±41
190 600
250
202±38
660
250
310
260
393±273 235±130 282±32
10.5 15.0
in mm/min.
