Surg Endosc DOI 10.1007/s00464-012-2309-1
and Other Interventional Techniques
Deep sedation in natural orifice transluminal endoscopic surgery (NOTES): a comparative study with dogs Mohammad Al-Haddad • Daniel McKenna • Jeff Ko • Stuart Sherman • Don J. Selzer • Samer G. Mattar • Thomas F. Imperiale • Douglas K. Rex • Attila Nakeeb • Seong Mok Jeong • Cynthia S. Johnson • Lynetta J. Freeman
Received: 19 December 2011 / Accepted: 2 April 2012 Ó Springer Science+Business Media, LLC 2012
Abstract Background Natural orifice transluminal endoscopic surgery (NOTES) has been mostly performed with the animal under general and inhalational anesthesia (IA-NOTES). To date, NOTES using propofol sedation (PS-NOTES) has not been investigated. This study aimed to assess the feasibility and safety of PS-NOTES for transgastric oophorectomy with carbon dioxide insufflation and to compare its success rates with those of conventional IA-NOTES. Methods In this prospective randomized study, NOTES oophorectomy was performed for 19 female dogs randomized to two conditions: PS (study group) and IA (control group). Sedation success rates (ability to visualize and resect ovaries without converting to IA), operative success rates (ability to resect and retrieve both ovaries in full using only NOTES), and vital parameters including hemodynamic and respiratory changes were documented.
Presented as a poster at the Digestive Disease Week held in Chicago, IL, USA between 7–10 May 2011. M. Al-Haddad (&) S. Sherman T. F. Imperiale D. K. Rex Department of Medicine, Division of Gastroenterology, Indiana University School of Medicine, 550 N University Boulevard, UH 4100, Indianapolis, IN 46202, USA e-mail:
[email protected] D. McKenna D. J. Selzer S. G. Mattar A. Nakeeb Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA J. Ko S. M. Jeong L. J. Freeman Purdue University School of Veterinary Medicine, West Lafayette, IN, USA C. S. Johnson Division of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA
Results In the PS-NOTES group (n = 9), the sedation success rate was 100 %. The operative success rate was 67 % (6 of 9 animals) compared with 80 % (8 of 10 animals) in the IA-NOTES group. No purposeful movement occurred during surgical manipulation and no respiratory or cardiovascular complications in occured the PS group. Heart rate (HR) and end-tidal carbon dioxide (ETCO2) were significantly higher in the PS group than in the IA group. Blood pressure (BP) was significantly higher in the PS group only during the middle part of the procedure. Only mild respiratory depression was noted in the PS group, as indicated by elevated but acceptable ETCO2. Elevations in BP and HR are thought to be related to elevated CO2 but did not appear to have an adverse impact on the course of the procedure. Recovery was uneventful for all the animals. Conclusion The use of PS-NOTES appears to be feasible, resulting in outcomes comparable with those for IA in dogs. Further studies are needed to determine the applicability of this concept in human NOTES. Keywords Inhalational anesthesia NOTES Oophorectomy Propofol sedation
Natural orifice transluminal endoscopic surgery (NOTES) has emerged as an ‘‘incisionless’’ transvisceral approach to the peritoneal cavity [1, 2]. The advantages that NOTES has over conventional surgery include less postoperative pain, fewer complications, decreased anesthesia requirements, accelerated patient recovery and return to normal function, and elimination of the risk for incisional herniation. Despite the identification of barriers to human uses in the first white paper [3], human NOTES applications continue to expand rapidly under investigational settings at a limited number of centers [4–15].
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Similar to laparoscopy, to date, human NOTES has been performed with the patient under general anesthesia for hemodynamic and ventilating reasons. The increased intraabdominal pressure from carbon dioxide (CO2) insufflation during laparoscopy adversely affects the hemodynamic stability of the patients by preventing venous return and reducing cardiac output [16]. Furthermore, the increased abdominal pressure displaces the diaphragm cephalad, reducing lung’s vital capacity during surgery and the early postoperative period [17–19]. Postoperative pain after laparoscopic procedures also could be at least partially attributed to insufflation of CO2. A proposed benefit of NOTES is that it requires minimal intraabdominal CO2 insufflation for visualization of structures and performance of procedures, and this combined with less abdominal trauma could partly explain the reduced need for postoperative analgesics in the clinical cases of NOTES cholecystectomy performed recently [20]. Our group has demonstrated that NOTES oophorectomy can be performed easily with the subject under a CO2 insufflation pressure of 10 to 12 mmHg, which is lower than the 14 mmHg of pressure required for the same procedure performed via laparoscopy [21]. Reduced insufflation pressures with NOTES procedures may preserve total lung capacity and maintain hemodynamic stability of the anesthetized patient without the need for assisted ventilation during the procedure [22]. We recently have demonstrated that NOTES oophorectomy allows earlier recovery than open and laparoscopic approaches [23, 24]. This has led to the assumption that sedation rather than general anesthesia may be feasible for NOTES due to the lower insufflation pressures compared with laparoscopy. Conscious sedation with or without local anesthesia has been used successfully on a limited scale in gynecologic and general surgical procedures [25–27]. A few NOTES case reports have introduced this concept for a percutaneous endoscopic gastrostomy (PEG) rescue in one case [28] and for peritoneoscopy in another case [29]. Propofol is a short-acting hypnotic agent with the advantage of rapid onset and offset of sedation as well as faster recovery of neuropsychiatric function [30–33]. Its safety and effectiveness for gastrointestinal (GI) procedures have been well described in large studies and endorsed by the various GI societies [30–32, 34–36]. Moreover, propofol use has facilitated the performance of complex endoscopic interventions in which traditional conscious sedation could be inadequate [37] and for high-risk patients [38]. Our hypothesis that NOTES can be performed with the patient under deep sedation was derived from previous observations of NOTES oophorectomy performed in dogs. This study aimed to assess the feasibility and safety of NOTES oophorectomy using propofol sedation (PS) compared with general inhalational anesthesia (IA).
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Methods Animal model The study was approved by Indiana University and Purdue University Institutional Animal Care and Use Committees (IACUC). A local animal shelter provided all the animals for the study. The study used 20 healthy female dogs weighing 11.6–26.4 kg. The animals were randomized into blocks with procedures consecutively performed on all the animals in the same group (PS or IA). One dog initially assigned to the PS group was excluded when the preoperative exam showed a spaying scar. At completion of the monitoring period, the dogs were returned to the same shelter for adoption. Study definitions Sedation success with PS-NOTES was defined as the ability to visualize and complete ovarian resection without respiratory or hemodynamic compromise necessitating conversion to general IA for completion of the procedure. Operative success was defined as complete resection and retrieval of both ovaries and gastric closure using the NOTES technique. Sedation, anesthesia, and monitoring All the animals were fasted for 24 h, and baseline values for heart rate, respiratory rate, and temperature were obtained. In the PS-NOTES group, a loading dose of propofol (3 mg/ kg) was administered intravenously (IV) followed by intermittent boluses (*1 mg/kg given every 1–2 min) for maintenance titered to a desired depth of sedation and vital parameters. The trachea was not intubated in this group, and a sampling catheter was placed in the proximal trachea to obtain a sample of expired air for end-tidal CO2. Supplemental oxygen also was provided, and the animals breathed spontaneously without ventilation. The a priori criteria for conversion from PS to IA included any sustained hemodynamic or respiratory compromise or excessive animal movement impairing the progress of the procedure. The dogs in the IA group were premedicated with acepromazine 0.02 mg/kg and hydromorphone 0.1 mg/kg followed by propofol induction (6 mg/kg, IV), endotracheal intubation, isoflurane anesthesia, and periodic manual ventilation. Mechanical ventilation then was used, and end-tidal CO2 was maintained between 35 and 40 mmHg. Overall and segment-specific procedure durations were tabulated, and vital signs including heart rate (HR), mean blood pressure (BP), respiratory rate (RR), oxygen saturation (SpO2) levels, and end-tidal partial pressure of CO2 (ETCO2) levels were recorded every 5 min in each group.
Surg Endosc
The animals were positioned in dorsal recumbency on a circulating water blanket to prevent anesthesia-induced hypothermia. Intravenous fluids were given during the procedure. Perioperative antibiotics (cefazolin 22 mg/kg IV every 2 h intraoperatively) were given, and aseptic procedures for clipping, preparing, and draping of the abdomen were followed. The endoscopes and other equipment underwent high-level disinfection after every use. An overtube (U.S. Endoscopy, Mentor, OH, USA) was used to reduce oral contamination. Both groups received carprofen (4 mg/kg, subcutaneously) preoperatively and 24 h postoperatively for analgesia. The dogs were given hydromorphone 0.05 mg/kg intramuscularly (IM) at the end of the surgical procedure for postoperative analgesia. A second dose of hydromorphone 0.05 mg/kg IM was administered 6 h after surgery. Postoperatively, each animal was monitored in recovery until its body temperature was higher than 37.2 °C. Postoperatively, the heart rate, respiratory rate, temperature, and indirect blood pressure were recorded every 6 h. The animals were monitored for 48 h for postoperative pain and complications before they were returned to the local shelter. NOTES procedure Starting with the IA group, NOTES oophorectomy was performed as we have previously described (Fig. 1) [24]. After a flexible therapeutic endoscope (Olympus GIF 2T160; Olympus America Inc., Center-Valley, PA, USA) had been passed into the stomach, cefazolin (1 g in 200 ml of normal saline) was instilled for 10 min and then aspirated. The gastrotomy was performed using an endoscopic balloon dilator (CRE Esophageal/Colonic Wire-Guided Balloon; Boston Scientific Corporation, Natick, MA, USA) advanced over a percutaneously inserted guidewire to create a 20 mm gastrotomy (Fig. 2) [24]. The endoscope was passed into the abdominal cavity, and air insufflation via the endoscope was provided (Fig. 3). Another 18-gauge catheter was placed in the peritoneal cavity, and CO2 insufflation was provided by a standard laparoscopic insufflator (Karl Storz Veterinary 183 Endoscopy America, Goletta, CA, USA) with the pressure set to 10 mmHg in addition to air from the endoscope. An alarm sounded when the intraabdominal pressure exceeded 10 mmHg or decreased to \8 mmHg. The animal’s position was adjusted to expose each ovary. A 3.0 9 4.5 cm hexagonal snare (AcuSnare; Cook Medical Inc., Bloomington, IN, USA) was passed through one of the working channels of the endoscope, and endoscopic grasping forceps (Polygrab Tripod; Olympus Endoscopy, Center-Valley, PA, USA) were passed into the second channel. Together, these instruments were used to elevate and loop the ovary (Fig. 4).
Fig. 1 Cartoon demonstrating the path of the endoscope as it exits the stomach and the consecutive steps for identifying, resecting, and retrieving each of the ovaries
Fig. 2 Freshly created gastrostomy pictured after deflation of the CRE balloon
The ovary was suspended to the abdominal wall using a surgical suture and inspected before initiation of cautery (Fig. 5). If needed, the ovary was released and resuspended to achieve the optimum resection level. The blood supply then was coagulated and transected using monopolar electrocautery at 20–40 W of blended current (Endostat II electrosurgical generator; Boston Scientific Corp.). The site was examined for hemorrhage. When encountered, hemorrhage was treated by attempted endoscopic cautery. Each
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Fig. 3 Abdominal wall as viewed by the endoscope after inflation of the peritoneal cavity with air. The endoscope is subsequently oriented caudad, and the left ovary is identified Fig. 5 Left ovary suspended to the abdominal wall using an external surgical suture to optimize visualization of the ovary and facilitate adjustment of the forceps grasp without dropping the ovary
Fig. 4 Endoscopic grasping forceps passed through a widely opened snare to elevate the ovary
ovary then was removed and examined to ensure complete resection (Fig. 6). If the ovary was not present in the tissue removed, another excision was performed. After removal of both ovaries, the gastrotomy was closed with prototype T fasteners using 2–0 nylon sutures and a knotting element (developed by Cook Medical, Bloomington, IN, USA; Fig. 7). Four T fasteners were placed around the incision, and opposite sutures were opposed and secured with the knotting element as previously described (Figs. 8, 9). Statistical analysis For the study, 10 animals were block-randomized to each group. With 10 animals per group, a two-sided, two-sample
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Fig. 6 Resected ovary (white part, upper half of the specimen) as seen after incision of the surrounding bursa
t test has 80 % power at the 0.05 level of significance to detect an effect size of 1.3 standard deviations. Due to variation in procedure times, only vital parameters taken during the first 145 min were used in the analyses. Two-sample t tests were used to compare baseline characteristics and procedure durations between the PS and IA groups. Repeated measures analysis of variance (ANOVA) was used to examine differences in mean blood pressure, heart and respiratory rates, SpO2 levels, and ETCO2 between the groups over time (Fig. 10, 11, 12, 13, and 14).
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Fig. 7 Plastic cap on the end of the endoscope providing a safety margin for deployment of the T-fasteners used to close the gastrostomy. A suture-knotting device (in purple) is used to unite each pair of opposing sutures by delivery of a small metallic binder
Fig. 9 Gastrostomy appearance after complete closure
Fig. 10 Mean blood pressure (mmHg) over time (min)
Results
Fig. 8 Cartoon illustrating the mechanism of gastric closure using the metallic binder to unite the sutures before they are cut with endoscopic scissors
Group-by-time interaction was included in each model to test for varying group differences over time. If the interaction was not significant, it was removed, and the final model included only the main effects. All p values less than 0.05 were considered significant. If the interaction term was significant, repeated measures ANOVA was performed using data from each 20-min interval of the procedure. If the interaction term was significant within a 20 min interval, two-sample t tests were performed at each time. All analyses were done using SAS version 9.3 (SAS, Cary, NC, USA).
The study was conducted between July and August 2010. The average total propofol dose in the PS-NOTES group was 1,178.6 mg, and the average infusion rate was 0.49 mg/kg/min. Sedation and operative outcomes The animals in the PS group weighed significantly less (p = 0.035) and had a significantly shorter distance to the gastroesophageal (GE) junction (p = 0.029) than the animals in the IA group. The procedure durations did not differ significantly between the groups except that significantly less time was required to close the gastric incision in the PS group than in the IA group (p = 0.021). In the PS group (n = 9), the sedation success rate was 100 %, and
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Fig. 13 Mean oxygen saturation (SpO2) (mmHg) over time (min) Fig. 11 Mean heart rate over time (min)
Fig. 12 Mean respiratory rate over time (min)
the operative success rate was 67 % (6 of 9 animals) compared with 80 % in the IA group (8 of 10 animals). The five operative failures were related to inadequate hemostasis of the ovarian pedicle in four animals (2 in each group) and inability to mobilize the ovary due to uterine size in one animal (PS group). These failures were resolved by conversion to open laparotomy with the animal under general IA. There was one episode of desaturation lasting less than 1 min that required removal and repositioning of the esophageal overtube in the first PS-NOTES animal. There was no purposeful movement during surgical manipulation, and no respiratory or cardiovascular adverse events were encountered in either group. Recovery was uneventful, with no need for rescue analgesia or postoperative complications in any animal. Vital parameters Heart rate and ETCO2 were significantly higher in the PS group (p = 0.002) than in the IA group (p = 0.036). There
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Fig. 14 Mean end-tidal carbon dioxide (CO2) (mmHg) over time (min)
were significant group-by-time interactions for mean blood pressure (p \ 0.001), respiratory rate (p \ 0.001), and SpO2 (p = 0.017) (Table 1). The mean blood pressure did not differ significantly between the groups during the first 20 min of the procedure or after 70 min (Table 2). The animals in the PS group had a significantly higher mean blood pressure than the animals receiving IA for 25–70 min (Table 3). The animals receiving PS had a significantly higher respiratory rate than the animals receiving IA during the first 20 min of the procedure (Table 1), but the respiratory rates did not differ significantly between the groups after 20 min (Tables 2, 3). During the first 20 min, and again between 50 and 70 min, the animals receiving PS had a significantly greater SpO2 than the animals receiving IA. At other times during the procedure, the SpO2 did not differ significantly between the groups
Surg Endosc Table 1 Comparison of vital parameters over time Vital parameter
Overall adjusted mean (SE)
p value
PS-NOTES
IA-NOTES
Interaction
Group
Time
BP (combined) (mmHg) HR (per min)
– 132.4 (5.0)
– 106.9 (4.7)
\0.001 0.693
– 0.002
– 0.001
–
–
0.036
0.011
RR (per min)
–
–
\0.001
SpO2 (%)
–
–
0.017
ETCO2 (mmHg)
58.6 (3.1)
48.9 (2.9)
0.621
SE standard error, PS propofol sedation, NOTES natural orifice transluminal endoscopic surgery, IA inhalational anesthesia, BP blood pressure, HR heart rate, RR respiratory rate, SpO2 oxygen saturation, ETCO2 end-tidal carbon dioxide
Table 2 Comparison of vital parameters over time when a significant interaction term was present
Vital parameter Time (min) BP (combined) (mmHg)
RR (per min)
SpO2 (%) SE standard error, PS propofol sedation, NOTES natural orifice transluminal endoscopic surgery, IA inhalational anesthesia, BP blood pressure, RR respiratory rate, SpO2 oxygen saturation
Overall adjusted mean (SE)
p value
PS-NOTES
Interaction
IA-NOTES
Group
Time
0–20
98.1 (6.7)
79.1 (6.3)
0.206
0.054
0.003
25–45
–
–
0.007
–
–
50–70
–
–
0.024
75–95
127.0 (5.1)
71.0 (4.8)
0.756
\0.001
0.198
100–120
120.1 (7.8)
77.4 (8.4)
0.398
0.003
0.042
125–145
110.8 (6.7)
77.3 (6.4)
0.142
0.022
0.336
0–20
16.8 (1.4)
12.0 (1.4)
0.248
0.026
0.752
25–45
15.3 (1.9)
14.7 (1.8)
0.069
0.815
0.132
\0.001
–
–
50–70
–
–
–
–
75–95
18.6 (1.8)
15.4 (1.7)
0.330
0.222
0.801
100–120 125–145
16.2 (2.4) 12.0 (3.0)
16.2 (2.6) 14.3 (3.4)
0.267 0.788
0.988 0.632
0.307 0.703
0–20
95.6 (0.5)
98.1 (0.5)
0.753
0.002
0.864
25–45
96.3 (0.4)
97.1 (0.3)
0.135
0.119
0.805
50–70
95.0 (0.5)
98.2 (0.4)
0.250
\0.001
0.912
75–95
95.9 (0.6)
97.5 (0.6)
0.433
0.076
0.316
100–120
96.7 (0.4)
97.6 (0.5)
0.358
0.237
0.001
125–145
96.4 (1.3)
96.3 (1.4)
0.240
0.951
0.490
Discussion This is the first animal study investigating the propofolonly approach in NOTES. Propofol appears to be feasible for performing NOTES oophorectomy in dogs without the need for airway intubation and with outcomes similar to those for inhalant general anesthesia. Further studies, however, are needed to determine the applicability of this concept for human NOTES. We have defined procedural success using two criteria (sedation and operative technique) to separate the failures due to operative techniques from those due to sedation inadequacy. The sedation success rate for NOTES was 100 %, and the operative success rates between the two groups were comparable (67 vs. 80 %). The operative failures were independent of the sedation or anesthesia
used and related to post-resection hemorrhage from the ovarian pedicle in four animals and due to a large postpartum uterus in one animal whose the ovaries could not be mobilized. The time spent attempting to secure hemostasis in those four animals resulted in variability in total procedure time between cases (Table 4). It can be argued that operative failures can lead to ‘‘sedation’’ failures because conversion to the open approach requires IA, although this failure would not be directly related to the mode of sedation or anesthesia. Such operative failures could be minimized in future human trials if dedicated NOTES platforms become available. We observed no body movements or significant compromise in vital functions that required rescue intubation or positive pressure ventilation for any animal in the PS group. Despite mildly elevated partial pressure of CO2
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Elevations in HR (throughout) and BP (25–70 min) were significant in the PS group, and we believe these are secondary to increased CO2 (in turn related to mild respiratory depression) rather than inadequate sedation. The elevated CO2 likely is related to permitting the animals to breathe spontaneously with no active ventilation. However, this has not resulted in any postprocedural delay of recovery or resumption of feeding and activity in any animal. It is possible that CO2 elevation could be a reflection of inadequate sedation, but we believe this is less likely because no inadvertent animal movement was noticed during the procedure. Despite the use of propofol doses adequate for performing oophorectomy (average, 0.49 mg/kg), we encountered no apnea, significant hypoxemia, or hypotension in the PS group. The use of propofol for GI sedation has been well characterized in the literature during the last decade. Findings have shown propofol administration by endoscopists or supervised experienced nurses to be feasible without a dramatic increase in the costs associated with using anesthesia services, resulting in better patient satisfaction than with conventional sedation [30–32]. In addition, a single intravenous agent for induction and maintenance of anesthesia [total intravenous anesthesia (TIVA)] without inhalational agents was introduced to clinical practice more than a decade ago [39–46]. Propofolbased TIVA provides rapid induction and recovery of anesthesia, facilitates rapid turnover of patients, and provides access to anesthesia services outside the conventional operating room setting where IA is unavailable. Nevertheless, TIVA usually is combined with analgesics and/or
(PCO2) indicating underlying hypoventilation, this has not resulted in any significant hypoxemia. In the same group, a moderate increase in intraperitoneal pressure (up to 10 mmHg) did not significantly compromise spontaneous ventilation in our experience. No procedure was interrupted due to respiratory or hemodynamic compromise. Table 3 Two-sample t test comparisons of vital parameters at each time Vital parameter
Time (min)
BP (combined) (mmHg)
RR (/min)
PSNOTES Mean (SE)
IANOTES Mean (SE)
p value
25
121.8 (9.0)
84.8 (7.8)
0.008
30
117.0 (5.5)
85.0 (6.3)
0.002
35
120.3 (5.8)
83.1 (8.0)
0.002
40
123.4 (6.0)
78.4 (7.5)
\0.001
45
129.1 (7.3)
78.5 (5.7)
\0.001
50
123.4 (5.3)
78.7 (6.7)
\0.001
55
127.1 (5.5)
79.5 (6.7)
\0.001
60
124.3 (6.1)
77.5 (5.7)
\0.001
65
125.1 (5.8)
75.3 (5.6)
\0.001
70
128.0 (4.7)
74.8 (6.5)
\0.001
50
13.6 (1.8)
15.8 (2.0)
0.417
55
13.8 (1.6)
14.7 (1.6)
0.688
60
14.9 (2.1)
14.5 (1.7)
0.886
65 70
16.9 (1.8) 16.4 (1.8)
13.1 (1.4) 14.6 (1.5)
0.119 0.436
PS propofol sedation, NOTES natural orifice transluminal endoscopic surgery, IA inhalational anesthesia, SE standard error, BP blood pressure, RR respiratory rate
Table 4 Baseline procedure-related data for the inhalational anesthesia and propofol groups Inhalational anesthesia group n
Mean
SD
Min
Propofol group Max
n
Mean
p value (t test)
SD
Min
Max
Weight (kg)
10
20.1
4.6
12.4
26.4
9
15.8
3.4
11.6
20
0.035
Distance to gastroesophageal junction (cm)
10
55.6
5.0
49
67
9
50.2
4.7
45
58
0.029
Induction to starting surgery (min)
10
39.4
15.2
23
60
9
47.7
7.7
37
60
0.162
Step 1a (min)
10
12.8
3.4
10
21
9
12.9
2.6
10
18
0.950
Step 2b (min)
10
8.3
5.2
3
20
9
6.6
5.1
2
16
0.470
Step 3b (min)
10
10.5
7.8
2
27
8
7.4
5.9
1
20
0.362
c
Step 4 (min)
9
4.1
2.8
1
10
8
9.4
7.6
1
22
0.099
Step 5c (min)
8
5.6
5.8
2
16
7
7.9
7.8
1
22
0.537
Step 6d (min)
8
23.4
5.0
17
31
6
17.0
3.6
13
22
0.021
10
132.6
45.0
88
227
9
126.9
40.5
75
192
0.776
Overall procedure time (min)
Min minimum, Max maximum, SD standard deviation Create access to the peritoneal cavity
a
b
Access and resect the left ovary
c
Access and resect the right ovary
d
Close the gastric incision
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benzodiazepines and muscle relaxants and typically requires endotracheal intubation with positive ventilation due to the risk of apnea associated with higher doses of anesthetics. None of these adjunct agents were used in the current study, so we labeled the intervention as ‘‘sedation’’ rather than anesthesia. Our data suggest that visceral resection can be performed with the subject under deep sedation alone, without the need for airway control, or combined with systemic analgesics or muscle relaxants. In our opinion, the lack of abdominal wall trauma (compared with open surgery) and reduced intraperitoneal pressure (compared with laparoscopy) is behind this observation in NOTES. Additionally, there is evidence that propofol-based anesthesia is associated with less increase in catecholamines, adrenocorticotropic hormone, and cortisol intra- and postoperatively than inhalational agents [47, 48] which could have reduced the cardiovascular burden of anesthesia in our study. The study had some limitations. First, the limited number of animals in each group may not have powered the study sufficiently for comparison of the particular outcomes we reported between the two groups, but we believe that such results would hold true in a larger sample due to the strength of the statistical significance. Second, the study used block randomization of 10 animals each, starting with the IA group. The impact of the timing in this case probably was minimal because our team achieved the ‘‘plateau’’ of the learning curve earlier, as we have demonstrated in a previous study [49]. For this study to be applicable to humans, we are assuming that abdominal wall compliance in humans and canines is similar. Nevertheless, few data exist to support this assumption. Moreover, factors that could potentially alter abdominal wall compliance in the dogs, such as previous pregnancy or weight loss, were largely unknown for the animals selected for this study. Additionally, we discovered after completion of the study that the two groups were not well matched by weight and that the animals in the IA group were significantly heavier. Because all the animals were provided by the local shelter, the investigators had limited control over the breed or the weight of the animals sent for oophorectomy. Finally, we did not closely track the recovery time in the IA group to allow comparison with the PS group because this study was designed mainly to assess sedation and outcomes. We have previously reported on earlier postoperative recovery and resumption of bowel function in NOTES oophorectomy [21]. If further studies demonstrate the feasibility of the described approach for humans, several advantages can be achieved. The PS-NOTES approach could provide a way to perform intraabdominal surgical interventions on an outpatient basis or in an environment such as a battlefield, in which a fully equipped hospital is not immediately
available. Additionally, this approach will provide further advantages by circumventing the need for bulky IA equipment, reducing costs due to a shorter hospital stay and facilitating outpatient procedures. Acknowledgments This study was funded by the NOSCAR (2010) and the Glen A. Lehman Endowed Chair Fund in Gastroenterology. Disclosures Mohammad Al-Haddad, Daniel McKenna, Jeff Ko, Stuart Sherman, Don J Selzer, Samer G. Mattar, Thomas F. Imperiale, Douglas K. Rex, Attila Nakeeb, Seong Mok Jeong, Cynthia S. Johnson, and Lynetta J Freeman have no conflicts of interest or financial ties to disclose.
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