My original impression of the title is that it might be religious though Cotterill has never gone heavy on theology in the past. It would also be out of character for Dr. Siri whose spirituality is based on his experiences rather than theology. It turned out that this title is a snarky political comment which is very consistent with the tone of the series.
The primary setting of the Dr. Siri mysteries is 20th century Laos, but there are occasional wanderings elsewhere. The Second Biggest Nothing contains flashbacks to past events in Siri's life in France and Vietnam. Just as Mme. Daeng's diary about her history in The Woman Who Wouldn't Die increased my appreciation of Siri's wife, the flashbacks in this book increased my already great appreciation for Siri.
Since I enjoy doing research on the books I read, I authenticated the central event of the French flashback taking place in 1932. It did indeed happen. Of course there's no mention of the fictional Dr. Siri having been a witness to it.
I thought that the 1956 Saigon and 1972 Hanoi flashbacks gave me additional insight into the Vietnam War from Siri's perspective as a medical officer.
There was a sub-plot involving spirits in The Second Biggest Nothing in which spirits were causing deaths among young Lao men. Siri mentions that something similar was happening among the Hmong, and named the Hmong spirit who was regarded as responsible for these deaths. I found an article dealing with this problem called Sudden Unexpected Nocturnal Death Syndrome which discussed it as a cross-cultural phenomenon though it seemed particularly notable among the Hmong. Dr. Siri resolved that sub-plot with a sensible solution.
The murderer of the main plotline did turn out to be connected to one of the flashbacks, but his identity was completely unexpected. There were also characters who played a surprising role in the resolution. I thought this was one of the better Dr. Siri novels.