Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report.

The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical testing, highlights gaps in current knowledge, and proposes areas for further research to enhance histocompatibility testing in support of solid organ transplantation. This report provides updates on topics discussed by the previous Sensitization in Transplantation: Assessment of Risk working groups and introduces 2 areas of exploration: non-human leukocyte antigen antibodies and utilization of human leukocyte antigen antibody testing measurement to evaluate the efficacy of antibody-removal therapies.

The allograft injury marker CXCL9 determines prognosis of anti-HLA antibodies after lung transplantation.

Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325 lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9 levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9 measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions.

Operational tolerance is not always permanent: A 10-year prospective study in pediatric liver transplantation recipients.

Immunosuppression withdrawal can be safely performed in select liver transplantation recipients, but the long-term outcomes and sustainability of tolerance have not been well studied. We completed a 10-year prospective, observational study of 18 pediatric liver transplantation recipients with operational tolerance to (1) assess the sustainability of tolerance over time, (2) compare the clinical characteristics of patients who maintained versus lost tolerance, (3) characterize liver histopathology findings in surveillance liver biopsies; and (4) describe immunologic markers in patients with tolerance. Comparator patients from two clinical phenotype groups termed "stable" and "nontolerant" patients were used as controls. Of the 18 patients with operational tolerance, the majority of patients were males (n = 14, 78%) who were transplanted for cholestatic liver disease (n = 12, 67%). Median age at transplantation was 1.9 (range, 0.6-8) years. Median time after transplantation that immunosuppression had been discontinued was 13.1 (range, 2.9-22.1) years. As many as 11 (61%) maintained tolerance for a median of 10.4 (range, 1.9-22.1) years, whereas 7 (39%) lost tolerance after a median of 3.2 (range, 1.5-18.6) years. Populations of T regulatory cells (%CD4+ CD25hi CD127lo ) were significantly higher in patients with tolerance (p = 0.02). Our results emphasize that spontaneous operational tolerance is a dynamic and nonpermanent state. It is therefore essential for patients who are clinically stable off immunosuppression to undergo regular follow-up and laboratory monitoring, as well as surveillance biopsies to rule out subclinical rejection.

Non-HLA AT1R antibodies are highly prevalent after pediatric intestinal transplantation.

The role of angiotensin II type-1 receptor (AT1R) antibodies in intestinal transplantation (ITx) is unclear. The aims were 1) to identify the prevalence of AT1R antibodies in pediatric ITx, compared to pediatric intestinal failure (IF), and 2) to determine whether AT1R antibodies were associated with graft dysfunction. 46 serum samples from 25 ITx patients (3 isolated ITx, 22 liver-inclusive ITx) were collected during routine visits >6 months apart and during episodes of graft dysfunction as a result of infectious enteritis or rejection. For comparison, samples were collected from 7 IF control patients. AT1R antibodies were considered positive for levels >17 U/mL. The median (range) AT1R antibody level for ITx patients was 40.0 U/mL (7.2-40.0), compared to 7.0 U/mL (5.7-40.0) for IF patients (p = .02). There was a trend toward higher prevalence of AT1R antibodies in ITx compared with IF patients (68% versus 29%, p = .09). Among ITx patients, the prevalence of AT1R antibodies was not different between periods of active graft dysfunction and normal health (83% versus 67%, p = .31). For 16 patients with >2 samples, AT1R antibodies remained positive in 67% cases, developed in 14% cases, disappeared in 10% cases, and remained negative in 10% cases. The changes in AT1R antibodies did not correlate with de/sensitizing events. This is the first study of AT1R antibodies in pediatric ITx. AT1R antibodies are highly prevalent after ITx and may be triggered by immune activation associated with the transplant. However, their pathogenicity and clinical utility remain in question.

Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.

The role of non-HLA antibodies in solid organ transplantation: a complex deliberation.

PURPOSE OF REVIEW: There is tremendous interest in understanding when, if, and how non-HLA antibodies contribute to allograft injury. Numerous non-HLA target antigens have been identified and sensitization to these targets have been associated with delayed allograft function, rejection, and allograft failure. This review focuses on the clinical utility of HLA antibody testing, highlighting the strengths and limitations of current clinical studies, and the need for defining characteristics to inform non-HLA antibody pathogenicity. RECENT FINDINGS: Clinical studies continue to show associations between non-HLA antibodies and rejection and reduced allograft survival across multiple transplanted organ types. The worst clinical outcomes continue to be observed among recipients testing positive for both non-HLA and donor-specific HLA antibodies. Mechanistic insights from both animal and clinical studies support a model in which tissue injury accompanied by an inflammatory environment influence non-HLA antibody formation and pathogenicity. SUMMARY: Immune triggers that lead to non-HLA antibody formation and pathogenicity are complex and poorly understood. The ability of non-HLA antibodies to mediate allograft injury may depend upon their affinity and strength (titer), target specificity, density of the target antigen, and synergy with donor-specific HLA antibodies.

Dual pO2/pCO2 fibre optic sensing film.

A fibre optic multi-sensor has been developed for biomedical sensing applications using a tip coating solution sensitive to both oxygen and carbon dioxide. An oxygen sensitive phosphorescence quenching complex based on platinum octaethylporphyrin (PtOEP) was combined with a carbon dioxide sensitive phosphorescence compound based on 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS). When excited by blue light (470 nm), the resultant coating had two fluorescent peaks at 515 nm (green) and 645 nm (red) which responded to partial pressure of CO2 and O2 respectively. The sensor was tested in vitro and shown to be able to measure CO2 and O2 simultaneously and in real time, with calibration constants of 0.0384 kPa-1 and 0.309 kPa-1 respectively. The O2 sensitive peak received some overlap from the 515 nm peak (0.38% of peak intensity) as well as some cross-sensitivity (maximum, 5.1 kPa pCO2 gave a measurement equivalent to 0.43 kPa of O2, a ratio of 0.08 : 1). However, these effects can be subtracted from measurements and no significant cross-sensitivity or overlap was seen in CO2 measurements from O2. This novel compound presents great potential for use in medical sensors and we expect it to be important to a wide range of future applications.

Acute antibody-mediated rejection in ABO-compatible pediatric liver transplant recipients: case series and review of the literature.

Acute AMR is well reported following ABO-incompatible LTx. However, it remains uncommon in ABO-compatible LTx. It typically presents with graft dysfunction ≤2 weeks post-LTx and is often associated with graft loss. We report the clinical presentation, treatment regimen, and outcome of six pediatric LTx recipients diagnosed with early acute AMR based on (i) clinical signs of graft dysfunction, (ii) histopathology indicative of acute injury ± C4d staining, and (iii) presence of HLA DSA. All patients developed elevated ALT and GGT ≤ 45 days post-LTx. All showed HLA class I (n=4) and/or II (n=6) DSA (peak MFI 6153-11 910). Four had de novo DSA, and two had preformed DSA. Five were initially diagnosed with ACR refractory to steroid therapy. Four exhibited resolution of graft dysfunction with AMR therapy. Two had refractory AMR-one was re-transplanted; the other was treated with eculizumab and showed improvement in graft function but later died due to a tracheostomy complication. Our case series suggests that AMR following ABO-compatible LTx may be under-diagnosed. The presentation can be variable, and treatment should be individualized. Eculizumab may be an option for refractory AMR. Ultimately, future multicenter studies are needed to better define diagnostic criteria, characterize optimal treatment, and assess long-term outcomes following liver AMR.

Fiber-optic fluorescence-quenching oxygen partial pressure sensor using platinum octaethylporphyrin.

The development and bench testing of a fiber-optic oxygen sensor is described. The sensor is designed for measurement of tissue oxygen levels in the mucosa of the digestive tract. The materials and construction are optimized for insertion through the mouth for measurement in the lower esophagus. An oxygen-sensitive fluorescence-quenching film was applied as a solution of platinum octaethylporphyrin (PtOEP) poly(ethyl methacrylate) (PEMA) and dichloromethane and dip coated onto the distal tip of the fiber. The sensor was tested by comparing relative fluorescence when immersed in liquid water at 37°C, at a range of partial pressures (0-101 kPa). Maximum relative fluorescence at most oxygen concentrations was seen when the PtOEP concentration was 0.1 g.L-1, four layers of coating solution were applied, and a fiber core radius of 600 µm was selected, giving a Stern-Volmer constant of 0.129 kPa-1. The performance of the sensor is suitable for many in vivo applications, particularly mucosal measurements. It has sufficient sensitivity, is sterilizable, and is sufficiently flexible and robust for insertion via the mouth without damage to the probe or risk of harm to the patient.

Investigation of peripheral photoplethysmographic morphology changes induced during a hand-elevation study.

A hand-elevation study was carried out in the laboratory in order to alter peripheral blood flow with the aim of increasing understanding of factors affecting the morphology of peripheral photoplethysmographic signals. Photoplethysmographic (PPG) signals were recorded from twenty healthy volunteer subjects during a hand-elevation study in which the right hand was raised and lowered relative to heart level, while the left hand remained static. Red and infrared (IR) PPG signals were obtained from the right and left index fingers using a custom-made PPG processing system. PPG features were identified using a feature-detection algorithm based on the first derivative of the PPG signal. The systolic PPG amplitude, the reflection index, crest time, pulse width at half height, and delta T were calculated from 20 s IR PPG signals from three positions of the right hand with respect to heart level (-50, 0, +50 cm) in 19 volunteers. PPG features were found to change with hand elevation. On lowering the hand to 50 cm below heart level, ac systolic PPG amplitudes from the finger decreased by 68.32 %, while raising the arm increased the systolic amplitude by 69.99 %. These changes in amplitude were attributed to changes in hydrostatic pressure and the veno-arterial reflex. Other morphological variables, such as crest time, were found to be statistically significantly different across hand positions, indicating increased vascular resistance on arm elevation than on dependency. It was hypothesized that these morphological PPG changes were influenced by changes in downstream venous resistance, rather than arterial, or arteriolar, resistance. Changes in hand position relative to heart level can significantly affect the morphology of the peripheral ac PPG waveform. These alterations are due to a combination of physical effects and physiological responses to changes in hand position, which alter vascular resistance. Care should be taken when interpreting morphological data derived from PPG signals and methods should be standardized to take these effects into account.

Glioma big potassium channel expression in human cancers and possible T cell epitopes for their immunotherapy.

Big potassium (BK) ion channels have several spliced variants. One spliced variant initially described within human glioma cells is the glioma BK (gBK) channel. This isoform consists of 34 aa inserted into the intracellular region of the basic BK ion channel. PCR primers specific for this inserted region confirmed that human glioma cell lines and freshly resected surgical tissues from glioblastoma multiforme patients strongly expressed gBK mRNA. Normal human brain tissue very weakly expressed this transcript. An Ab specific for this gBK isoform confirmed that human glioma cells displayed this protein in the cell membrane, mitochondria, Golgi, and endoplasmic reticulum. Within the gBK region, two putative epitopes (gBK1 and gBK2) are predicted to bind to the HLA-A*0201 molecule. HLA-A*0201-restricted human CTLs were generated in vitro using gBK peptide-pulsed dendritic cells. Both gBK1 and gBK2 peptide-specific CTLs killed HLA-A2⁺/gBK⁺ gliomas, but they failed to kill non-HLA-A2-expressing but gBK⁺ target cells in cytolytic assays. T2 cells loaded with exogenous gBK peptides, but not with the influenza M1 control peptide, were only killed by their respective CTLs. The gBK-specific CTLs also killed a variety of other HLA-A*0201⁺ cancer cells that possess gBK, as well as HLA-A2⁺ HEK cells transfected with the gBK gene. Of clinical relevance, we found that T cells derived from glioblastoma multiforme patients that were sensitized to the gBK peptide could also kill target cells expressing gBK. This study shows that peptides derived from cancer-associated ion channels maybe useful targets for T cell-mediated immunotherapy.

Differential expression of interferon-γ and chemokine genes distinguishes Rasmussen encephalitis from cortical dysplasia and provides evidence for an early Th1 immune response.

BACKGROUND: Rasmussen encephalitis (RE) is a rare complex inflammatory disease, primarily seen in young children, that is characterized by severe partial seizures and brain atrophy. Surgery is currently the only effective treatment option. To identify genes specifically associated with the immunopathology in RE, RNA transcripts of genes involved in inflammation and autoimmunity were measured in brain tissue from RE surgeries and compared with those in surgical specimens of cortical dysplasia (CD), a major cause of intractable pediatric epilepsy. METHODS: Quantitative polymerase chain reactions measured the relative expression of 84 genes related to inflammation and autoimmunity in 12 RE specimens and in the reference group of 12 CD surgical specimens. Data were analyzed by consensus clustering using the entire dataset, and by pairwise comparison of gene expression levels between the RE and CD cohorts using the Harrell-Davis distribution-free quantile estimator method. RESULTS: Consensus clustering identified six RE cases that were clearly distinguished from the CD cases and from other RE cases. Pairwise comparison showed that seven mRNAs encoding interferon-γ, CCL5, CCL22, CCL23, CXCL9, CXCL10, and Fas ligand were higher in the RE specimens compared with the CD specimens, whereas the mRNA encoding hypoxanthine-guanine phosphoribosyltransferase was reduced. Interferon-γ, CXCL5, CXCL9 and CXCL10 mRNA levels negatively correlated with time from seizure onset to surgery (P <0.05), whereas CCL23 and Fas ligand transcript levels positively correlated with the degree of tissue destruction and inflammation, respectively (P <0.05), as determined from magnetic resonance imaging (MRI) T2 and FLAIR images. Accumulation of CD4+ lymphocytes in leptomeninges and perivascular spaces was a prominent feature in RE specimens resected within a year of seizure onset. CONCLUSIONS: Active disease is characterized by a Th1 immune response that appears to involve both CD8+ and CD4+ T cells. Our findings suggest therapeutic intervention targeting specific chemokine/chemokine receptors may be useful in early stage RE.

Continuation of immunosuppression vs. immunosuppression weaning in potential repeat kidney transplant candidates: a care management perspective.

Management of immunosuppression in patients with a failing or failed kidney transplant requires a complete assessment of their clinical condition. One of the major considerations in determining immunosuppression is whether or not such an individual is considered a candidate for re-transplantation. Withdrawal of immunosuppression in a re-transplant candidate can result in allosensitization and markedly reduce the chances of a repeat transplant. In this review, we summarize the effects of immunosuppression reduction on HLA sensitization, discuss the impacts of allosensitization in these patients, and explore reduction protocols and future directions. Risks of chronic immunosuppression, medical management of the failing allograft, and the effect of nephrectomy are covered elsewhere in this issue.

Virtual and Reality: An Analysis of the UCLA Virtual Crossmatch Exchanges.

The "virtual" crossmatch (VXM) has become a critical tool to predict the compatibility between an organ donor and a potential recipient. Yet, nonstandardized laboratory practice can lead to variability in VXM interpretation. Therefore, UCLA's VXM Exchange survey was designed to understand factors that influence the variability of VXM prediction in the presence of HLA donor-specific antibody (DSA). Thirty-six donor blood samples and 72 HLA reference sera were sent to 35 participating laboratories to perform HLA antibody testing, flow crossmatch (FXM), and VXM from 2014 to 2019, consisting of 144 T/B-cell FXM pairs and 112 T/B-cell VXM pairs. In the FXM survey, 86% T-cell FXM and 84% B-cell FXM achieved >80% concordance among laboratories. In the VXM survey, 81% T-cell VXM and 80% VXM achieved >80% concordance. The concordance between FXM and VXM was 79% for T cell and 87% for B cell. The consensus between VXM and FXM was high with strong DSA. However, significant variability was observed in sera with (1) very high titer antibodies that exit prozone effect; (2) weak-to-moderate DSA, particularly in the presence of multiple weak DSAs; and (3) DSA against lowly expressed antigens. With the increasing use the VXM, standardization and continuous learning via exchange surveys will provide better understanding and quality controls for VXM to improve accuracy across all centers.

Preservation of Antiviral Immunologic Efficacy Without Alloimmunity After Switch to Belatacept in Calcineurin Inhibitor-Intolerant Patients.

Introduction: Belatacept has shown potential for prevention of rejection after kidney transplantation, given its demonstration of reduced nephrotoxicity in combination with absence of significant incidence of rejection. However, concerns have been raised regarding increased risk of viral infection. Methods: We set out to explore the impact of the switch to belatacept on alloimmune and antiviral immunity through the study of patients switched from calcineurin inhibitor (CNI) to belatacept within 3 months of kidney transplantation compared with a matched cohort of control patients on a CNI-based regimen. Results: After the switch to belatacept, immune phenotyping demonstrated a decrease in naive and an increase in terminally differentiated effector memory (TMRA) T cells, with no significant difference compared with control patients. Donor-specific immune response, measured by intracellular cytokine staining (ICS), did not change significantly either by single or double cytokine secretion, but it was associated with the appearance of donor-specific antibody (DSA) in the control but not the belatacept cohort (P = 0.039 for naive and P = 0.002 for TMRA subtypes). Increased incidence of de novo DSA development was observed in the control group (P = 0.035). Virus-specific immune response, as measured by ICS in response to cytomegalovirus (CMV) or Epstein-Barr virus (EBV), was similar in both groups and stable over time. Conclusion: We found that belatacept use was associated with an absence of alloreactivity without impact on immune phenotype, while preserving the antiviral immune response, for patients switched from a CNI-based regimen. In parallel, the antiviral immune response against CMV and EBV was preserved after the belatacept switch (clinicaltrials.gov: NCT01953120).

Evaluation of electrical and optical plethysmography sensors for noninvasive monitoring of hemoglobin concentration.

Completely noninvasive monitoring of hemoglobin concentration has not yet been fully realized in the clinical setting. This study investigates the viability of measuring hemoglobin concentration noninvasively by evaluating the performance of two types of sensor using a tissue phantom perfused with a blood substitute. An electrical sensor designed to measure blood volume changes during the cardiac cycle was used together with an infrared optical sensor for detection of erythrocyte-bound hemoglobin. Both sensors demonstrated sensitivity to changes in pulse volume (plethysmography). The electrical sensor produced a signal referred to as capacitance plethysmograph (CPG) a quantity which was invariant to the concentration of an infrared absorbing dye present in the blood substitute. The optical sensor signal (photoplethysmograph) increased in amplitude with increasing absorber concentration. The ratio PPG:CPG is invariant to pulse pressure. This quantity is discussed as a possible index of in vivo hemoglobin concentration.

Variability in Donor-Derived Cell-Free DNA Scores to Predict Mortality in Heart Transplant Recipients - A Proof-of-Concept Study.

BACKGROUND: Over the last decade, expanding use of molecular diagnostics in heart transplantation has allowed implementation of non-invasive surveillance strategies for monitoring allograft health. The commercially available HeartCare platform combines the AlloMap gene expression profiling assay and the AlloSure donor-derived cell-free DNA test (dd-cfDNA). Beyond their established use for assessment of rejection, evidence is building for predictive utility, with the longitudinal AlloMap Variability score previously shown to correlate with the risk of future rejection, graft dysfunction, re-transplantation, or death. In this single-center, retrospective pilot study, we evaluated the performance of a novel AlloSure Variability metric in predicting mortality in a cohort of heart transplant recipients. METHODS: Seventy-two adult heart transplant recipients with at least 3 concurrent AlloMap/AlloSure results were included. Demographic, clinical, imaging, and laboratory parameters were captured. Variability was defined as the standard deviation of longitudinal AlloMap/AlloSure results. A Cox multivariable adjusted proportional hazards model was used to evaluate the variability metrics as predictors of mortality. Associations between AlloMap/AlloSure variability and donor specific antibody (DSA) status were also assessed. RESULTS: A total of 5 patients (6.9%) died during a median follow-up of 480 days. In a univariate Cox proportional hazards model, higher AlloSure variability (HR 1.66, 95%CI 1.14 - 2.41), but not AlloMap variability or the cross-sectional AlloSure/AlloMap results was associated with increased mortality risk. Longitudinal AlloSure variability was also higher among patients with both preformed DSA and those developing de novo DSA. CONCLUSION: Our results suggest that increased variability of dd-cfDNA in heart transplant patients is associated with both mortality risk and the presence of donor specific antibodies. These findings highlight the added value of longitudinal data in the interpretation of AlloMap/AlloSure scores in this population and open the door to larger studies investigating the utility of these metrics in shaping post-transplant clinical care paradigms.

An in vivo investigation of photoplethysmographic signals and preliminary pulse oximetry estimation from the bowel using a new fiberoptic sensor.

BACKGROUND: The continuous monitoring of splanchnic organ oxygen saturation could make the early detection of inadequate tissue oxygenation feasible, reducing the risk of hypoperfusion, severe ischemia, multiple organ failure, and, ultimately, death. Current methods for assessing splanchnic perfusion have not been widely accepted for use in the clinical care environment. In an attempt to overcome the limitations of the current techniques, a new fiberoptic photoplethysmographic (PPG)/pulse oximetry sensor was developed as a means of assessing splanchnic organ perfusion during surgery in humans. METHODS: A new fiberoptic splanchnic pulse oximeter and an optically identical fiberoptic finger pulse oximeter have been developed. Simultaneous PPG signals and preliminary estimates of arterial oxygen saturation from the bowel (small and large) and finger were obtained in 17 patients (3 men and 14 women) undergoing open laparotomy. RESULTS: Good quality PPG signals were obtained from the small and large bowel and from the finger in all patients (lower 95% confidence limit for the proportion was 0.64). Comparisons of blood oxygen saturation values acquired when using the splanchnic and the finger fiberoptic sensors and a commercial finger pulse oximeter indicated that there was no statistically significant difference between them (all P>0.454). A Bland and Altman plot of the difference between blood oxygen saturation values from the bowel fiberoptic pulse oximeter and the fiberoptic finger pulse oximeter against their mean showed that the limits of agreement between the 2 pulse oximeters were -3.8% and 4.2% for small bowel measurements, and -3.4% and 4.3% for large bowel measurements. The 95% prediction interval for the difference between the 2 devices was between -4.2% and 4.7%. CONCLUSION: This study demonstrated that good quality PPG signals can be obtained from the bowel using a new fiberoptic sensor. Further evaluation is required to determine whether fiberoptic pulse oximetry of the bowel may provide a suitable method for monitoring splanchnic perfusion.

Investigation of photoplethysmographic signals and blood oxygen saturation values obtained from human splanchnic organs using a fiber optic sensor.

OBJECTIVE: A reliable, continuous method of monitoring splanchnic organ oxygen saturation could allow for the early detection of malperfusion, and may prevent the onset of multiple organ failure. Current monitoring techniques have not been widely accepted in critical care monitoring. As a preliminary to developing a continuous indwelling device, this study evaluates a new handheld fiber optic photoplethysmographic (PPG) sensor for estimating the blood oxygen saturation (SpO(2)) of splanchnic organs during surgery. METHODS: A fiber optic splanchnic PPG sensor, instrumentation system and virtual instrument were developed to facilitate PPG and SpO(2) measurement from splanchnic organs. Following Local Research Ethics Committee approval, the sensor was evaluated on seventeen ASA 1 and 2 patients undergoing open laparotomy. PPG signals were obtained from the large bowel, small bowel, liver and stomach. Simultaneous PPG signals from the finger were also obtained using an identical fiber optic sensor. RESULTS: Good quality PPG signals with high signal-to-noise (SNR) ratios were obtained from all splanchnic sites under investigation. Analysis of the ac and dc amplitudes of the red and infrared PPG signals showed there to be a statistically significant difference between PPG signals obtained from splanchnic organs with those obtained from the finger (using fiber optic sensors). Estimated SpO(2) values from the splanchnic organs show good agreement with those obtained from the finger using both a fiber optic sensor and a commercial device. Furthermore, the results of a Bland and Altman analysis indicate that fiber optic splanchnic pulse oximetry, particularly of the bowel, may provide a suitable method for monitoring splanchnic organ perfusion. CONCLUSION: The evaluation of a new fiber optic sensor on anaesthetized patients undergoing laparotomy demonstrated that good quality PPG signals and SpO(2) estimates can be obtained from splanchnic organs. Such a sensor may provide a useful tool for the intraoperative assessment of splanchnic perfusion.