Group Title: BMC Surgery
Title: Non-invasive monitoring of tissue oxygenation during laparoscopic donor nephrectomy
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Title: Non-invasive monitoring of tissue oxygenation during laparoscopic donor nephrectomy
Physical Description: Book
Language: English
Creator: Crane, Nicole
Pinto, Peter
Hale, Douglas
Gage, Frederick
Tadaki, Doug
Kirk, Allan
Levin, Ira
Elster, Eric
Publisher: BMC Surgery
Publication Date: 2008
 Notes
Abstract: BACKGROUND:Standard methods for assessment of organ viability during surgery are typically limited to visual cues and tactile feedback in open surgery. However, during laparoscopic surgery, these processes are impaired. This is of particular relevance during laparoscopic renal donation, where the condition of the kidney must be optimized despite considerable manipulation. However, there is no in vivo methodology to monitor renal parenchymal oxygenation during laparoscopic surgery.METHODS:We have developed a method for the real time, in vivo, whole organ assessment of tissue oxygenation during laparoscopic nephrectomy to convey meaningful biological data to the surgeon during laparoscopic surgery. We apply the 3-CCD (charge coupled device) camera to monitor qualitatively renal parenchymal oxygenation with potential real-time video capability.RESULTS:We have validated this methodology in a porcine model across a range of hypoxic conditions, and have then applied the method during clinical laparoscopic donor nephrectomies during clinically relevant pneumoperitoneum. 3-CCD image enhancement produces mean region of interest (ROI) intensity values that can be directly correlated with blood oxygen saturation measurements (R2 > 0.96). The calculated mean ROI intensity values obtained at the beginning of the laparoscopic nephrectomy do not differ significantly from mean ROI intensity values calculated immediately before kidney removal (p > 0.05).CONCLUSION:Here, using the 3-CCD camera, we qualitatively monitor tissue oxygenation. This means of assessing intraoperative tissue oxygenation may be a useful method to avoid unintended ischemic injury during laparoscopic surgery. Preliminary results indicate that no significant changes in renal oxygenation occur as a result of pneumoperitoneum.
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BMC Surgery B.1ole Central


Technical advance


Non-invasive monitoring of tissue oxygenation during laparoscopic
donor nephrectomy
Nicole J Crane', Peter A Pinto2, Douglas Hale3, Frederick A Gage4,
Doug Tadakil, Allan D Kirk5, Ira W Levin6 and Eric A Elster*1,4,6,7


Address: 'Naval Medical Research Center, Combat Casualty Care, Silver Spring, MD 20910, USA, 2National Institutes of Health, National Cancer
Institute, Urologic Oncology, Bethesda, MD 20892, USA, 3University of Florida, College of Medicine, General Surgery Residency Program,
Jacksonville, FL, 32209, USA, 4Department of Surgery, National Naval Medical Center, Bethesda, MD 20892, USA, 5Emory University Hospital,
Emory Transplant Center, Atlanta, GA 30322, USA, 6National Institutes of Health, National Institute of Diabetes and Digestive and Kidney
Diseases, Laboratory of Chemical Physics, Bethesda, MD 20892, USA and 7Department of Surgery, Uniformed Services University, University of
Health Sciences, Bethesda, MD 20892, USA
Email: Nicole J Crane Nicole.Crane@med.navy.mil; Peter A Pinto pintop@mail.nih.gov; Douglas Hale Douglas.Hale@jax.ufl.edu;
Frederick A Gage Frederick.Gage@med.navy.mil; Doug Tadaki Doug.Tadaki@med.navy.mil; Allan D Kirk allan.kirk@emoryhealthcare.org;
Ira W Levin iwl@helix.nih.gov; Eric A Elster* Eric.Elster@med.navy.mil
* Corresponding author



Published: 17 April 2008 Received: 23 October 2007
BMC Surgery 2008, 8:8 doi:10.I 186/1471-2482-8-8 Accepted: 17 April 2008
This article is available from: http://www.biomedcentral.com/1471-2482/8/8
2008 Crane et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Abstract
Background: Standard methods for assessment of organ viability during surgery are typically
limited to visual cues and tactile feedback in open surgery. However, during laparoscopic surgery,
these processes are impaired. This is of particular relevance during laparoscopic renal donation,
where the condition of the kidney must be optimized despite considerable manipulation. However,
there is no in vivo methodology to monitor renal parenchymal oxygenation during laparoscopic
surgery.
Methods: We have developed a method for the real time, in vivo, whole organ assessment of tissue
oxygenation during laparoscopic nephrectomy to convey meaningful biological data to the surgeon
during laparoscopic surgery. We apply the 3-CCD (charge coupled device) camera to monitor
qualitatively renal parenchymal oxygenation with potential real-time video capability.
Results: We have validated this methodology in a porcine model across a range of hypoxic
conditions, and have then applied the method during clinical laparoscopic donor nephrectomies
during clinically relevant pneumoperitoneum. 3-CCD image enhancement produces mean region
of interest (ROI) intensity values that can be directly correlated with blood oxygen saturation
measurements (R2 > 0.96). The calculated mean ROI intensity values obtained at the beginning of
the laparoscopic nephrectomy do not differ significantly from mean ROI intensity values calculated
immediately before kidney removal (p > 0.05).
Conclusion: Here, using the 3-CCD camera, we qualitatively monitor tissue oxygenation. This
means of assessing intraoperative tissue oxygenation may be a useful method to avoid unintended
ischemic injury during laparoscopic surgery. Preliminary results indicate that no significant changes
in renal oxygenation occur as a result of pneumoperitoneum.




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Background
In the past 10 years the use of living donor kidneys have
markedly increased and in 2003 surpassed deceased
donors as the predominant source of donor organs [1].
Laparoscopic donor nephrectomy has become a major
driving force in increasing the acceptance of living dona-
tion. Laparoscopic donor nephrectomy (LDN) is thought
to have several potential advantages over open donor
nephrectomy (ODN) [1,2]. Namely, laparoscopic proce-
dures require a shorter hospital stay, decreased amounts
of analgesia, allow for a faster return to work and provide
improved cosmesis. However, disadvantages of laparo-
scopic surgery include slightly longer warm ischemic
times, and increased incidences of delayed graft function,
the later thought to be the result of tissue hypoxia from
pneumoperitoneum associated hypoperfusion and organ
manipulation [1,2]. These issues, while minor in most
donors, are increasingly problematic in situations utiliz-
ing older donors, or organs intended for use in very small
children [3,4]. Many technical aspects of laparoscopic
donation have been developed to minimize organ
ischemic injury, and several parameters have been moni-
tored to indirectly assess the general tolerance of pneu-
moperitoneum, including cardiac output, stroke volume,
mean arterial pressure, urine output, systemic vascular
resistance and end-tidal CO2. All of the methodologies are
limited by their inability to assess the organ directly. The
most direct measurement would be that of whole organ
oxygenation. Unfortunately, to date there has not been a
method to evaluate tissue oxygenation laparoscopically in
a time frame that is clinically relevant. The ability to intra-
operatively monitor renal paranchyemal oxygenation
would be useful in a number of clinical situations in
which prompt resolution may have a dramatic effect. One
such an example is encountered when during the course
of the operation the blood supply to the organ becomes
impaired by the technical manuevers done during dissec-
tion (i.e., approaching the vessels from the posterior
aspect). Prompt recognition of decreased oxygenation
would allow for repositioning of the kidney and re-estab-
lishment of blood flow. Other examples include the deter-
mination of secondary renal arteries and the
establishment of a baseline acceptable pneumoperiote-
num, potentially useful in older donors.

In this report, we describe the development of a means of
directly assessing organ oxygenation during laparoscopic
surgery. Spectroscopic information obtained by a stand-
ard 3-CCD camera used in laparoscopic surgery is proc-
essed thereby providing real time feedback to the surgeon
using equipment readily available in any standard laparo-
scopic operating suite.


Methods
Algorithm: 3-CCD Detector Analysis
Images of porcine nephrectomies and human LDNs were
used to calculate mean intensity values from the 3-CCD
camera as described previously [5,6]. Briefly, the human
nephrectomies were recorded using a Storz laparoscopic
tower (Tuttlingen, Germany), equipped with a 3-CCD
camera. The porcine nephrectomies were recorded using
an Olympus laparoscopic tower (Orangeburg, NY, USA)
coupled to a Stryker 3-CCD camera (San Jose, CA, USA)
without the laparoscope attachment. Individual frames of
the recorded video were extracted as TIFF (tagged image
format file) files as seen in Figure la. Using Matlab soft-
ware (Natick, MA, USA) the blue CCD response (Figure
Ic) was subtracted from the red CCD response (Figure ib)
[6]. This difference has been directly correlated with the
spectral response of hemoglobin in both the blue and red
regions of the visible spectrum [6]. The resulting image
(Figure Id) is plotted in a modified color scale. An intense
red color indicates pixels receiving the most signal from
the red CCD and an intense blue color indicates pixels
receiving the least amount of signal from the red CCD.
Finally, the calculated image is overlaid onto the original
TIFF image (Figure le), allowing complete visual registry
along with enhancement.

Testing: Validation using a Porcine Model
Porcine experiments (n = 4) were performed as a valida-
tion of the sensitivity and correlation of 3-CCD mean
intensity values with actual blood and tissue oxygenation.
Porcine laparotomies, as part of an animal protocol
approved by the Institutional Animal Care and Use Com-
mittee, were used to assess the extent of ischemic injury
(i.e. decreased tissue oxygenation) incurred by reduced
fractions of inspired oxygenation (FiO2) during surgery.
Standard open surgical techniques were employed to
exposure the kidney and renal hilum. Mean region of
interest (ROI) values were calculated from the video
images of the surgery collected using the 3-CCD camera
and compared to measured arterial and venous oxygen
saturation values (saO2 and svO2).

The 3-CCD camera and the tower light were mounted to
the overhead operating room light such that both kidneys
were evenly illuminated and in the field of view. The frac-
tion of inspired oxygenation was decreased incrementally
(~100%, ~50%, ~30%, ~20%, 9%) during the determina-
tion. After each decrease in FiO2, the kidney was allowed
to equilibrate for approximately 15 minutes. Renal oxy-
gen tension (pO2) was measured directly by an OxyLite
fluorescence needle probe (Oxford Optronics Ltd.,
Oxford, UK) in the superior pole of the kidneys (Figure 2).
Fluorescence measurements confirm changes in blood
oxygen saturation in the kidney itself as a result of reduced
FiO2. Blood was also drawn from the aorta and renal veins


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140
120
100
80
60
40
20
0


250
:00

150

100

60


150

100

50


Figure I
Laparoscopic donor nephrectomy. (a) Image of kidney extracted from DVD as a .tiff file. (b) Red CCD response, plotted
in grayscale. (c) Blue CCD response, plotted in grayscale. (d) Red CCD response minus blue CCD response, set to special
color scale. (e) Calculated CCD response image overlaid onto the original image at 55% transparency.


following equilibrium and immediately analyzed for
saO2 and svO2 using a portable blood gas analyzer (iStat,
Abbott Point of Care Inc., East Windsor, NJ, USA).

For each different FiO2 level, mean values for the ROIs in
the images were calculated from rectangles comprised of
900-4,500 pixels. While rectangle sizes varied for each
image, the dimensions of a rectangle at a particular loca-
tion in the image remained relatively consistent from
image to image; the orientation of the kidney changed lit-
tle throughout the determination.

Implementation: Laparoscopic Donor Nephrectomy
Healthy renal donors (n = 9) were enrolled in a National
Institutes of Health Institutional Review Board (NIH IRB)
approved protocol to assess outcomes during and after liv-
ing donor nephrectomy as well as one of several NIH IRB


approved protocols to assess allograft function. LDN was
performed using previously described techniques with a
continuous pneumoperitoneum of 15 mmHg [7]. Renal
allografts were then transplanted using standard surgical
techniques. All nine kidneys were left kidneys, with a sin-
gle artery, vein, and ureter, which were immediately
flushed with cold University of Wisconsin solution prior
to transplantation. Donor and recipient demographics are
outlined in Table 1.

For each case and time series of extracted frames, mean
values for the ROIs in the images were calculated from rec-
tangles containing at least 625-44,000 pixels. Rectangle
size was not consistent image to image because the orien-
tation of the kidney was constantly changing. Glare
proved troublesome by contributing false blue regions in
the subtracted images; thus, regions of glare were


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30 40
Elapsed Time (min)


Figure 2
Renal parenchymal oxygen tension (p02) measured
via a fluorescence probe, as the fraction of 02 (FiO2)
is reduced over 65 minutes. The FiO2 is indicated with
dashed arrows. The times of blood draws, where blood gas
measurements were made (sO2), are indicated by BD.




neglected when calculating mean values for the ROIs prior
to normalization.

Statistical Method
The student's t-test was used to determine significant dif-
ferences between ROI mean values. Means were consid-
ered significantly different with p-values less than 0.05.
For comparisons of mean ROI values determined during
the pig nephrectomies, a paired t-test for sample means
was applied. For comparisons of mean ROI values calcu-
lated within the same human surgical case, an unpaired,
two-tailed t-test with equal variances was applied.


Results
Spectroscopic Evidence
I. Animal Model
The described technique was first tested and validated
using a porcine model. A fluorescent needle probe (OxyL-
ite) was used to monitor changes in renal oxygenation,
alongside 3-CCD assessment. In Figure 2, the solid line
follows pO2 levels as the FiO2 level, indicated over the
duration of the dashed arrows, is decreased. Figure 2 dem-
onstrates a drop in the pO2 in the kidney each time the
percentage of inspired oxygen is decreased, followed by a
region of little change equilibrationn). Each venous blood
draw (BD) is marked by a small increase in pO2; as the
blood is drawn from the renal vein, fresh blood flows
from the renal artery into the kidney, creating a temporary
increase in tissue oxygenation.

At 100% inspired oxygen, saO2 is 100% with mean ROI
values from the detector data of 0.66 0.02, 0.68 0.03,
0.60 0.03, and 0.51 0.05, for kidneys 1 through 4. Sim-
ilar mean ROI values were observed for ~50% FiO2 with
100% saO2 (0.70 0.01, 0.71 0.03, 0.57 0.02, and
0.55 + 0.06, for kidneys 1 through 4). For kidneys 1 and
2, at 28% FiO2 and an saO2 of 98%, the mean ROI values
calculated were 0.70 + 0.02 and 0.69 + 0.02, still largely
unchanged from 100 and 50% FiO2. Similar values were
observed for kidneys 3 and 4 at 21% FiO2 and an saO2 of
91% (0.57 0.01 and 0.52 0.06). Though the drop in
FiO2 from ~50% to 28% and 21% is significant, FiO2's of
28% and 21% are similar to room air; thus, a large drop
in mean ROI values from ~50% FiO2 to 28% and 21%
FiO2 is not expected. There is, however, a definite decrease
in the mean ROI values determined for kidneys 1 and 2
with an FiO2 of 18% and saO2 of 83% (0.64 0.03 for
both kidneys). The mean ROI values drop significantly
when the FiO2 is decreased to ~9% (0.43 0.03, 0.44 +
0.03, 0.36 0.02, and 0.32 0.03, for kidneys 1-4) when
compared to previous mean ROI values (p = 0.005). When
the calculated ROI values are plotted against the saO2 for


Table I: Patient Demographics

Case Donor Age (yrs)


1
2
3
4
5
6
7
8
9
Mean


48
49
27
53
39
26
42
28
22
37.1 + 11.6


BMI (kg/m2) Gender OR time (min)


26.01

23.20
26.23
26.79
23.30
37.08
22.74
20.69
25.76 + 5.03


female
female
female
male
male
male
female
female
male


300
240
220
300
240
340
280
355
385
296 + 156


EBL (ml) Fluid (ml)* Urine (ml)


700
400
100
300
400
< 50
150
200
100
294 + 204


8600
6200
6000
6600
8500
4400
3700
5800
5800
6178 1662


1400
3000
1400
1900
2400
S100
900
1400
1665
1685 660


BMI body mass index; OR operating room; EBL estimated blood loss
* Fluid was lactated ringers in all cases.


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Figure 3
Linear relationship of calculated mean normalized
ROI (region of interest) values and measured venous
s02 as the FiO2 is decreased from 100% to 8% in four
different kidneys. R2 = 0.9722 (0), 0.9854 (0), 0.9624 (A)
and 0.9801 (0).


each kidney, there is a clear linear relationship between
ROI values and saO2 measurements, as indicated by Fig-
ure 3.

2. Role of Pneumoperitoneum
This technique was then applied to nine human LDN
cases to determine if pneumoperitoneum reduced paren-
chymal oxygenation. Interval monitoring of kidneys
showed stable oxygenation without evidence of signifi-
cant hypoxia. The mean values for the ROIs are presented
chronologically for each case in Figure 4. Various time
points are examined, where most gaps in the sampling
intervals were less than 15 minutes. For case 5, however,
unambiguous image data of the kidney was not obtaina-
ble for a period of approximately 95 minutes. The dura-
tion over which image frames were collected also varied.
Case 1 sampled the shortest period, with a duration of
~16 minutes, while case 9 has the longest sampling dura-
tion, ~ 170 minutes. Cases 1 through 9 appear to fluctuate
slightly but not significantly, in spite of differing normal-
ized ROI mean intensities. The normalized ROI mean
intensity values for case 5 decreased over time with respect
to the starting point (79.78 + 6.62 versus 56.20 10.44,
44.98 13.71, 56.67 16.05, 55.07 7.24, 32.84
12.76), but returned to a comparable value by the end of
the sampling period (79.78 6.62 versus 68.64 7.83).

Table 2 displays the mean starting ROI values which are
compared to the mean ending ROI values for each case
with the corresponding p-values. No statistically signifi-
cant differences exist between the starting and the ending
mean ROI values for all cases, with p-values all greater


.kidne 1 k1dn 1 kde 3- I k.n-Yz


BMC Surgery 2008, 8:8


than 0.05. The mean starting ROI value for all cases, 70.21
12.36, is comparable to the mean ending ROI value for
all cases, 66.43 10.53 (p = 0.49). The small fluctuation
in values implies that the oxygenation of the kidney is rel-
atively stable with an intraabdominal pressure of no more
than 15 mm Hg. Note, intrapatient comparison of mean
ROI values is not performed due to variability in abdom-
inal illumination from case to case and variability in dura-
tion of pnuemoperitoneum from case to case.

While not presented in this manuscript, we have also
examined laparoscopic partial nephrectomies, where
complete hilar clamping or renal arterial clamping is per-
formed, and so, we have explored variation in oxygena-
tion as a direct result of surgically-induced
vasoconstriction. We do in fact see the mean ROI values
decrease after clamping and then return to baseline ROI
values after reperfusion (p _< 0.05 in all cases).

Clinical Findings
All spectroscopic evidence for lack of change in kidney
oxygenation during pneumoperitoneum is supported by
standard clinical methods for assessing kidney function.
Immediate graft function was seen in all recipients. The
mean one day pre-operative donor serum creatinine level
is 0.9 + 0.2 mg/dl. The mean post-operative recipient
serum creatinine levels for post-operative days 1, 5 and 20
were 5.2 + 1.6 mg/dl, 1.6 0.4 mg/dl, and 1.5 + 0.4 mg/
dl, indicative of brisk post transplant function. Individual
case values are shown in Table 3. The mean post-operative
recipient BUN levels, considered normal between 8 and
20 mg/dl, (shown in Table 4) for post-operative days 1, 5
and 20 are 36 13 mg/dl, 25 8 mg/dl, and 17 5 mg/
dl. With the exception of case 9, the recipient serum creat-
inine levels and recipient BUN levels were all within nor-
mal limits by post-operative day 20.

Discussion
This manuscript reports, for the first time, the use of a 3-
CCD camera to detect hypoxia in vivo and in doing so,
introduces a potential means of avoiding unintended
hypoxic injury during laparoscopic surgery. In addition to
demonstrating that tissue oxygenation is not impaired
during routine donor nephrectomy, the study highlights a
novel and useful method for intraoperative functional
imaging. As such, this study supports current laparoscopic
methodology with CO2 pneumoperitoneum and intro-
duces a method with broad potential as an intraoperative
monitoring device.

We chose the open porcine model so that pneumoperito-
neum would not be a variable when considering the effect
of blood oxygenation on the mean ROI values calculated
from the 3-CCD camera. While the equipment employed
in this study is used in an open fashion, it is designed for


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1:31:53 1:37:38 1:43:24


1:08:48


2:06:24


3:04:00


10C

80

60

40

20
e
1:28:48 2:26:24 3:24:00
100

80

60

40

20

9


0:54:24


1:23:12


1:52:00


1:44:24 2:13:12 2:42:00 3:10:48


2:29:24 2:58:12 3:27:00 3:55:48











f
0:57:24 1:26:12 1:55:00


h
1:06:24 1:35:12 2:04:00 2:32:48


80

60

40

20

C1
1:18:00 2:15:36 3:13:12 4:10:
Time (hr: min: sec)


Figure 4
The normalized mean ROI values for nine donor laparoscopic nephrectomies: (a-i) case 1-9, respectively.





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Table 2: Mean intensity normalized ROI values. Mean intensity variables, laparoscopic nephrectomies require a longer
normalized ROI values of both the start and end time points for warm ischemia time than open nephrectomies [81, which
each case. All p-values are above 0.05 and indicate the mean ROI .
values for the start and end time points are not significantly may result in additional ischemia as a result of the pneu-
different. moperitoneum [9]; thus, an evaluation of the kidney's
viability becomes vital. It is clearly beneficial to be able to
Case Mean ROI &* Mean ROI a* p-value monitor the status of the kidney in real time.


Starting point


48.40
54.88
72.42
84.27
79.78
81.17
75.50
62.41
73.09


5.60
14.56
5.51
3.38
6.62
7.24
3.37
10.58
2.49


End point


44.48
65.02
61.17
75.58
68.64
75.98
78.96
60.29
67.74


* a = one standard deviation

laparoscopic incorporation. An obvious model for altered
tissue oxygenation would have been clamping the renal
hilum; however, in our hands, it has been extremely diffi-
cult to partially clamp the hilum in a controlled fashion
(progressive hilar clamping) or to allow the kidney to
reperfuse in a controlled and partial manner. Without
being able to control the tissue oxygenation or deoxygen-
ation, we could not reliably collect enough data points for
a clear correlation. Thus, the decreasing FiO2 model was
chosen for our validation experiment. This model directly
enabled correlation of oxygen delivery with 3-CCD mean
ROI values.

Outside of clinical studies or animal models, intraopera-
tive assessment of tissue oxygenation during LDN is cur-
rently limited to visualization of the parenchyma with the
naked eye. Although kidney function, in general, has been
monitored by creatinine and/or tissue pathology, results
from both techniques are not obtained immediately. Fur-
ther, the use of these assays requires a significant amount
of time following injury. In general, as a result of technical


Current techniques to assess the kidney during surgery
include a non-contact laser tissue blood flowmeter
(NCLBF) [10], pulse oximetry, fluorescein, laser autofluo-
rescence imaging [111, measuring erythrocyte velocity
[12], and fluorescence oxygen tension measurements
[13,14]. In a study by Ando and coworkers, NCLBF was
compared with pulse oximetry and fluorescein for the
assessment of ischemic tissue. It was determined that
NCBLF outperformed pulse oximetry and fluorescein in
accuracy and sensitivity in predicting the viability of
ischemic bowel [10]. Pulse oximetry and fluorescein have
a high risk of failure for detecting tissue necrosis in addi-
tion to a poor accuracy rate for evaluation purposes. The
disadvantage of a technique like NCLBF is that the meas-
urement is made via a pencil probe, appropriate for open
surgery but not laparoscopic surgery. Laser autofluores-
cence imaging operates on the assumption that autofluo-
rescence changes with 335 nm excitation are attributed to
NADH which accumulates in tissue during ischemia [ 11].
While the technique shows promising results and allows
for real time in vivo imaging, this method requires special
instrumentation and is not easily converted to a format
for use with a laparoscopic tower. Measurement of eryth-
rocyte velocity using a magnifying endoscope [12] is the
only above-mentioned technique that could be easily
applied during a laparoscopic surgery. However, the pen-
cil-lens probe of the endoscope samples and evaluates
only a small portion of the tissue during a single measure-
ment. Evaluation of the kidney as a whole would require
a large number of sampling points, proving inefficient in
a time limited scenario. While the OxyLite probe is very
effective for sampling tissue oxygenation within the tissue
itself [13,14], it suffers from the same limitations as the


Table 3: Donor and recipient serum creatinine levels (pre- and post-operative). Normal serum creatinine levels are < 1.6 mg/dl.


Donor Serum Creatinine (mg/dl)


Pre-op day I


Recipient Serum Creatinine (mg/dl)


Post-op day I


Pre-op day 5

1.5
1.7
1.8
1.2
1.1
1.3
1.4
2.4
1.9


Post-op day 10

1.7
1.6
1.6
1.0
0.9
1.3
1.6
1.7
2.0


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Table 4: Recipient blood urea nitrogen values at post-operative
days I, 5 and 20. Normal BUN is 8-20 mg/dl.


Case


Recipient Blood Urea Nitrogen (mg/dl)

Post-op day I Post-op day 5 Post-op day 20


erythrocyte velocity measurements; the needle probe
allows for only spot measurements, not global tissue oxy-
genation measurements. Thus, currently, there are no
techniques that are well suited for the diagnosis of tissue
viability during laparoscopic surgery.

The technique presented in this manuscript presents real-
time capability with straight forward incorporation of
additional software and computer interfacing. Real-time
function will not require additional hardware or equip-
ment that is not readily available in the operating suite.
While glare proves troublesome for some images, inclu-
sion of polarizing optics directly into the laparoscope
itself would obviate this problem. Though the technique
probes the surface of tissue and is not able to detect tissue
oxygenation beneath fatty regions, as in LDN, this obsta-
cle is typically negated by the need for surgical dissection.
Similarly, bloody operating fields are only problematic if
the entire region of interest is obscured; several small,
exposed regions are sufficient for calculating mean ROI
values. In addition, surface assessment of tissue oxygena-
tion appears to reflect whole organ oxygenation as evi-
denced by the large animal data presented herein.

Conclusion
We present preliminary results for a technique that has the
potential to diagnose tissue ischemia in real time and in
an organ specific manner during laparoscopic surgery. In
addition, using this technique we demonstrate that sus-
tained pneumoperitoneum at standard levels (15 mmHg)
in a small case series did not have adverse effects on tissue
oxygenation as measured by this methodology and sub-
stantiated by the clinical course. Although the calculations
presented in this study were performed outside of the
laparoscopic system, efficient programming will allow
automatic, real time incorporation of the calculation to
the laparoscopic images. While the clinical utility of this
method is still unknown, we recognize that an expanded
study, involving a significantly greater number of cases


than presented here, would allow the development of a
training set by which threshold values for tissue end-point
resuscitation could be established. The developed training
set would be the foundation for a clinical validation
study. Another consideration for the clinical validation
would be the addition of a range of pneumoperitoneum
pressures, including pressures greater than 15 mm Hg.
Furthermore, this technique may be broadly applicable to
provide an indicator of organ ischemia during all laparo-
scopic surgeries.

Competing interests
The authors) declare that they have no competing inter-
ests.

Authors' contributions
NJC and EAE conceived the study. IWL participated in the
study design. NJC developed the technique and per-
formed all data analysis. NJC and EAE drafted the manu-
script. PAP, DH, ADK, and EAE performed the surgeries.
FG and DT participated in study coordination. All authors
read and approved the final manuscript.

Acknowledgements
The authors would like to thank Kambiz Tajkarimi, Ben McHone, Jack Liu
and Marie McHenry for their assistance with the porcine model in this
experiment. The views expressed in this article are those of the author and
do not necessarily reflect the official policy or position of the Department
of the Navy, Department of Defense, nor the U.S. Government. This work
was prepared as part of the official duties of a military service member (E.
E.). Title 17 U.S.C. 105 provides that 'Copyright protection under this title
is not available for any work of the United States Government.' Title 17
U.S.C. 101 defines a U.S. Government work as a work prepared by a mil-
itary service member or employee of the U.S. Government as part of that
person's official duties. We also acknowledge support from the intramural
program of the National Institute of Diabetes and Digestive and Kidney Dis-
eases, National Institutes of Health.

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